Comprehending conformational changes in EmrE, multidrug transporter at different pH: insights from molecular dynamics simulations.

EmrE is a small multidrug resistance (SMR) pump of antiparallel topology that confers resistance to a broad range of polyaromatic cations in Escherichia coli. Atomic-level understanding of conformational changes for the selectivity of substrate and transport of a diverse array of drugs through the smallest known efflux pumps is crucial to multi-drug resistance. Therefore, the present study aims to provide insights into conformational changes during the transport through EmrE transporter at different pH. Molecular dynamics simulations have been carried out on the complete structure of EmrE in the absence of substrate. Computational analyses such as secondary structure, principal component, dynamic cross-correlation matrix, and hydrogen bond calculations have been performed. Analysis of MD trajectories in this study revealed pH-dependent interactions that influenced the structural dynamics of EmrE. Notably, at high pH, Glu14 and Tyr60 in both monomers formed electrostatic interactions, while these interactions decreased significantly at a low pH. Interestingly, a kink at helix 3 (H3) and dual open conformation of EmrE at low pH were also observed in contrast to a closed state discerned towards the periplasmic side at high pH. Significant interactions between C-terminal residues and residues at the edge of H1 & Loop1 and H3 & Loop3 were identified, suggesting their role in stabilizing the closed conformation of EmrE at the periplasmic end under high pH conditions. The present study enhances our understanding of EmrE's conformational changes, shedding light on the pH-dependent mechanisms that are likely to impact its function in multi-drug resistance.Communicated by Ramaswamy H. Sarma.

Radon and thoron exhalation rate in the soil of Western Haryana, India.

This study reports the exhalation rates of radon and thoron from surface soil collected from 60 rural sites of district Hisar, Haryana, India. The exhalation rates of Rn222 (radon) and Rn220 (thoron) were measured by portable SMART RnDuo (AQTEK SYSTEMS) using a mass accumulation chamber which was equipped with a scintillation material-coated cell. Dose rates due to natural gamma radiations ranged from 0.526 to 1.139 mSv y-1. The Rn222 mass exhalation rate in soil samples varied from 0.14 to 94.65 mBq kg-1 h-1. Thoron surface exhalation rates ranged from 46.42 to 619.88 Bq m-2 h-1. This study gives an idea about the differences in Rn222 and Rn220 exhalation at different locations which may be due to variations in geological features of the locations and characteristics of the topsoil. The findings show that usage of study area soil as building material is safe.

Long-Lived States Provide Insights from NMR into the ß-Cyclodextrin Drug Assemblies.

In the last two decades, extending spin memory in NMR has been used for several purposes. Long-lived states (LLS) or singlet states are one of the first spin memory enhancement techniques used. LLS have the potential to extract structural information and intra- and intermolecular interactions of complex systems other than studying slow phenomenon. The motional regime of ß-cyclodextrin (ß-CD) drug inclusion complexes generally lies in the intermediate region, where ωτc ≈ 1, and the standard methods of studying these interactions, i.e., NOE and chemical shift monitoring, suffer from insufficient output information. The sensitivity of LLS toward the environmental changes is utilized here to gain insights into the drug assemblies formed by ß-CD. One can use change in relaxation of LLS to study the structural changes during complexation. The examples of ß-CD with the drugs indomethacin, paracetamol, gliclazide, and CI-933 (a precursor 4-methoxybenzamide) were studied. Indomethacin, paracetamol, and 4-methoxybenzamide show strong interaction through the para-substituted benzene ring, unlike gliclazide. Relaxation of LLS in ß-CD-drug complexes is modeled using standard Redfield Relaxation Theory. Computational studies performed support the experimental observations. Docking and molecular dynamics simulation provided the explanation of the relaxation properties of these drug molecules.

Convergence of two global regulators to coordinate expression of essential virulence determinants of Mycobacterium tuberculosis.

Cyclic AMP (cAMP) is known to function as a global regulator of Mycobacterium tuberculosis gene expression. Sequence-based transcriptomic profiling identified the mycobacterial regulon controlled by the cAMP receptor protein, CRP. In this study, we identified a new subset of CRP-associated genes including virulence determinants which are also under the control of a major regulator, PhoP. Our results suggest that PhoP as a DNA binding transcription factor, impacts expression of these genes, and phosphorylated PhoP promotes CRP recruitment at the target promoters. Further, we uncover a distinct regulatory mechanism showing that activation of these genes requires direct recruitment of both PhoP and CRP at their target promoters. The most fundamental biological insight is derived from the inhibition of CRP binding at the regulatory regions in a PhoP-deleted strain owing to CRP-PhoP protein-protein interactions. Based on these results, a model is proposed suggesting how CRP and PhoP function as co-activators of the essential pathogenic determinants. Taken together, these results uncover a novel mode of regulation where a complex of two interacting virulence factors impact expression of virulence determinants. These results have significant implications on TB pathogenesis.

Assessment of association between smoking and all-cause mortality among Malaysian adult population: Findings from a retrospective cohort study.

INTRODUCTION: Smoking is a known risk factor for many chronic diseases. Illness and death due to smoking are a significant public health burden in many countries. This study aims to address the information gap in smoking-related mortality in Malaysia by estimating the risk of cardiovascular disease and all-cause mortalities due to smoking among Malaysian adults. METHODS: We analyzed data on 2525 respondents, aged 24-64 years, of the Malaysian Non-Communicable Disease Surveillance survey conducted September 2005 to February 2006. Mortality records from the Malaysian National Registration Department were linked to the MYNCDS-1 data to determine respondents' mortality status over 12 years from 2006 to 2018. Associations between smoking and all-cause mortalities were assessed using Cox proportional hazards regression with adjustments for non-communicable disease and sociodemographic and lifestyle factors. RESULTS: The prevalence of daily smoking was 21.2% (95% CI: 19.0-23.7). During the 31668 person-years follow-up, 213 deaths from all causes occurred, where 68 deaths were among smokers (13.2%), and 452 were among non-smokers (6.3%). Smoking was associated with a significantly increased risk of all-cause mortality (adjusted hazard ration, AHR=1.79; 95% CI: 1.12- 2.97). These associations remained significant after excluding mortalities in the first two years of follow-up. CONCLUSIONS: Daily smoking is associated with a significantly higher risk of all-cause death. Behavioral and pharmacological smoking cessation interventions should be intensified among smokers to reduce the risk of mortality.

Role of Cys-298 in specific recognition of glutathione by aldose reductase.

Aldose reductase (AR) is an NADPH-dependent oxidoreductase that is well-studied for its role in Diabetes Mellitus. Glutathione conjugated aldehydes are efficiently catalysed by AR. We have employed molecular dynamics simulations to investigate the dynamics of a glutathione analog, γ-glutamyl-S-(1,2-di-carboxyethyl)-cysteinyl-glycine (DCEG), into the binding pocket of AR. Study revealed that backbone nitrogens of Ala-299 and Leu-300 form a tiny pocket gated by thiol group of Cys-298. The glycine moiety of DCEG was able to displace the thiol group of Cys-298 to make hydrogen bond interactions with backbone of Ala-299, Leu-300, and Leu-301. This study provides the details of the dynamic interactions of DCEG in the binding pocket of AR, and shall aid in the design/discovery of differential inhibitors against AR.Communicated by Ramaswamy H. Sarma.

Structurally disordered C-terminal residues of GTP cyclohydrolase II are essential for its enzymatic activity.

GTP cyclohydrolase II (GCHII) is one of the rate limiting enzymes in riboflavin biosynthesis pathway and is shown to be a potential drug target for most of the pathogens. Previous biochemical and structural studies have identified the active site residues and elucidated the steps involved in the catalytic mechanism of GCHII. However, the last ∼20-25 C-terminal residues of GCHII remains unstructured in all the crystal structures determined to date and their role in the catalytic activity, if any, remains elusive. Therefore, to understand the role of these unstructured C-terminal residues, a series of C-terminal deletion mutants of GCHII from Helicobacter pylori (hGCHII) were generated and their catalytic activity was compared with its wild-type. Surprisingly, none of the C-terminal deletion mutants shows any enzymatic activity indicating that these are essential for GCHII function. To get additional insights for such loss of activity, homology models of full-length and deletion mutants of hGCHII in complex with GTP, Mg2+, and Zn2+ were generated and subjected to molecular dynamics simulation studies. The simulation studies show that a conserved histidine at 190th position from the unstructured C-terminal region of hGCHII interacts with α-phosphate of GTP. We propose that His-190 may play a role in the hydrolysis of pyrophosphate from GTP and in releasing the product, DARP. In summary, we demonstrate that the unstructured C-terminal residues of GCHII are important for its enzymatic activity and must be considered during rational drug designing. Communicated by Ramaswamy H. Sarma.

Tobacco use and other aspects related to smoking among school-going adolescents aged 13-15 years in Malaysia: Analysis of three cross-sectional nationally representative surveys in 2003, 2009 and 2016.

INTRODUCTION: Periodic surveys on tobacco use patterns and other aspects of tobacco use among school-going adolescents in Malaysia provide information on the effectiveness of anti-smoking measures implemented. However, such information is limited in Malaysia. We investigated the prevalence of smoking and other related aspects among middle-secondary school students in Malaysia from the years 2003-2016 to fill this gap. METHODS: We analyzed data from the Global Youth Tobacco Survey (GYTS) 2003, GYTS 2009, and the Tobacco and Electronic Cigarette Survey among Malaysia Adolescents (TECMA) 2016. The surveys employed multistage sampling to select representative samples of adolescents attending secondary school in Malaysia. Data were collected using a pre-validated self-administered anonymous questionnaire adopted from the GYTS. RESULTS: Between 2003 and 2016, major changes occurred in which there were reductions in the prevalence of ever smoking, current smoking, and susceptibility to smoking. Reductions were also observed in exposure to SHS in public places and in the home. The proportion of school-going adolescents who support a ban on smoking in public places increased between 2013 to 2016, and there was a significant reduction in the proportion of respondents that were offered 'free' cigarettes by tobacco company representatives. However, there was no difference in the proportion of adolescents who initiated smoking before the age of 10 years and current smokers seeking advice to quit smoking across the time period. CONCLUSIONS: Our study indicates that the smoking policies and measures have been effective in reducing smoking prevalence, secondhand smoke exposure, and access to cigarettes, among school-going adolescents in Malaysia. However, measures to reduce smoking initiation and increase smoking cessation need to be strengthened to reduce the burden of smoking-related diseases in Malaysia in the long-term.

Deciphering the Structural Enigma of HLA Class-II Binding Peptides for Enhanced Immunoinformatics-based Prediction of Vaccine Epitopes.

Vaccines remain the most efficacious means to avoid and eliminate morbid diseases associated with high morbidity and mortality. Clinical trials indicate the gaining impetus of peptide vaccines against diseases for which an effective treatment still remains obscure. CD4 T-cell-based peptide vaccines involve immunization with antigenic determinants from pathogens or neoplastic cells that possess the ability to elicit a robust T helper cell response, which subsequently activates other arms of the immune system. The available in silico predictors of human leukocyte antigen II (HLA-II) binding peptides are sequence-based techniques, which ostensibly have balanced sensitivity and specificity. Structural analysis and understanding of the cognate peptide and HLA-II interactions are essential to empirically derive a successful peptide vaccine. However, the availability of structure-based epitope prediction algorithms is inadequate compared with sequence-based prediction methods. The present study is an attempt to understand the structural aspects of HLA-II binders by analyzing the Protein Data Bank (PDB) complexes of pHLA-II. Furthermore, we mimic the peptide exchange mechanism and demonstrate the structural implication of an acidic environment on HLA-II binders. Finally, we discuss a structure-guided approach to decipher potential HLA-II binders within an antigenic protein. This strategy may accurately predict the peptide epitopes and thus aid in designing successful peptide vaccines.

Clinical and epidemiologic profile of the initial COVID-19 patients at a tertiary care centre in India.

COVID-19 has now become a pandemic. It has spread from Wuhan, China, in December 2019 to a large number of countries within three months. The objective of this work is to report the initial experience with epidemiologic and clinical features, as well as with the management of COVID-19 patients in India. This is a descriptive case series of the first 21 COVID-19 infected patients confirmed with polymerase chain reaction (PCR) and admitted to a tertiary care centre in India from 01.02.2020 to 19.03.2020. Clinical, laboratory, and radiologic data were collected, including age, sex, nationality, travel history, symptoms, duration of stay, and comorbidities. The mean age of the population was 40.3 years with a male preponderance. Thirteen (62%) patients had recent travel history outside India in the previous 30 days, two thirds of whom had travelled to Italy. The most common symptoms were fever and cough (42.9%) followed by sore throat, headache and breathlessness. Vital and laboratory parameters were preserved in all patients and none of them required ventilatory support. Among the first 21 patients diagnosed with COVID-19 infection in India, the typical clinical presentation consisted in a mild upper respiratory tract infection predominantly affecting the young male population. One patient required supplemental oxygen. All patients recovered with no residual symptoms.   *The Safdarjung Hospital COVID 2019 working group: Nitesh Gupta, Sumita Agrawal, Pranav Ish, Suruchi Mishra, Rajni Gaind, Ganapathy Usha, Balvinder Singh, Manas Kamal Sen, Shibdas Chakrabarti (Consultant and Head, Pulmonary Medicine); NK Gupta (Professor, Pulmonary medicine); Dipak Bhattacharya (Consultant, Pulmonary medicine); Rohit Kumar (Assistant Professor, Pulmonary Medicine); Siddharth R. Yadav (Assistant Professor, Pulmonary Medicine); Rushika Saksena (Specialist, Microbiology); Rojaleen Das (Assistant Professor, Microbiology); Vikramjeet Dutta (Assistant Professor, Microbiology); Anupam Kr Anveshi (Senior Resident, Microbiology); Santvana Kohli (Assistant Professor, Anaesthesiology); Naveen KV (Assistant Professor,  Anaesthesiology); Amandeep Jaswal (Assistant Professor, Anaesthesiology).

HSPMdb: a computational repository of heat shock protein modulators.

Heat shock proteins (Hsp) are among highly conserved proteins across all domains of life. Though originally discovered as a cellular response to stress, these proteins are also involved in a wide range of cellular functions such as protein refolding, protein trafficking and cellular signalling. A large number of potential Hsp modulators are under clinical trials against various human diseases. As the number of modulators targeting Hsps is growing, there is a need to develop a comprehensive knowledge repository of these findings which is largely scattered. We have thus developed a web-accessible database, HSPMdb, which is a first of its kind manually curated repository of experimentally validated Hsp modulators (activators and inhibitors). The data was collected from 176 research articles and current version of HSPMdb holds 10 223 entries of compounds that are known to modulate activities of five major Hsps (Hsp100, Hsp90, Hsp70, Hsp60 and Hsp40) originated from 15 different organisms (i.e. human, yeast, bacteria, virus, mouse, rat, bovine, porcine, canine, chicken, Trypanosoma brucei and Plasmodium falciparum). HSPMdb provides comprehensive information on biological activities as well as the chemical properties of Hsp modulators. The biological activities of modulators are presented as enzymatic activity and cellular activity. Under the enzymatic activity field, parameters such as IC50, EC50, DC50, Ki and KD have been provided. In the cellular activity field, complete information on cellular activities (percentage cell growth inhibition, EC50 and GI50), type of cell viability assays and cell line used has been provided. One of the important features of HSPMdb is that it allows users to screen whether or not their compound of interest has any similarity with the previously known Hsp modulators. We anticipate that HSPMdb would become a valuable resource for the broader scientific community working in the area of chaperone biology and protein misfolding diseases. HSPMdb is freely accessible at http://bioinfo.imtech.res.in/bvs/hspmdb/index.php.

ImmtorLig_DB: repertoire of virtually screened small molecules against immune receptors to bolster host immunity.

Host directed therapies to boost immunity against infection are gaining considerable impetus following the observation that use of antibiotics has become a continuous source for the emergence of drug resistant strains of pathogens. Receptors expressed by the cells of immune system play a cardinal role in initiating sequence of events necessary to ameliorate many morbid conditions. Although, ligands for the immune receptors are available; but their use is limited due to complex structure, synthesis and cost-effectiveness. Virtual screening (VS) is an integral part of chemoinformatics and computer-aided drug design (CADD) and aims to streamline the process of drug discovery. ImmtorLig_DB is a repertoire of 5000 novel small molecules, screened from ZINC database and ranked using structure based virtual screening (SBVS) against 25 immune receptors which play a pivotal role in defending and initiating the activation of immune system. Consequently, in the current study, small molecules were screened by docking on the essential domains present on the receptors expressed by cells of immune system. The screened molecules exhibited efficacious binding to immune receptors, and indicated a possibility of discovering novel small molecules. Other features of ImmtorLig_DB include information about availability, clustering analysis, and estimation of absorption, distribution, metabolism, and excretion (ADME) properties of the screened small molecules. Structural comparisons indicate that predicted small molecules may be considered novel. Further, this repertoire is available via a searchable graphical user interface (GUI) through http://bioinfo.imtech.res.in/bvs/immtor/ .

Morbid Sequences Suggest Molecular Mimicry between Microbial Peptides and Self-Antigens: A Possibility of Inciting Autoimmunity.

Understanding etiology of autoimmune diseases has been a great challenge for designing drugs and vaccines. The pathophysiology of many autoimmune diseases may be attributed to molecular mimicry provoked by microbes. Molecular mimicry hypothesizes that a sequence homology between foreign and self-peptides leads to cross-activation of autoreactive T cells. Different microbial proteins are implicated in various autoimmune diseases, including multiple sclerosis, human type 1 diabetes, primary biliary cirrhosis and rheumatoid arthritis. It may be imperative to identify the microbial epitopes that initiate the activation of autoreactive T cells. Consequently, in the present study, we employed immunoinformatics tools to delineate homologous antigenic regions between microbes and human proteins at not only the sequence level but at the structural level too. Interestingly, many cross-reactive MHC class II binding epitopes were detected from an array of microbes. Further, these peptides possess a potential to skew immune response toward Th1-like patterns. The present study divulges many microbial target proteins, their putative MHC-binding epitopes, and predicted structures to establish the fact that both sequence and structure are two important aspects for understanding the relationship between molecular mimicry and autoimmune diseases. Such findings may enable us in designing potential immunotherapies to tolerize autoreactive T cells.

Eukaryotic-type serine/threonine kinase mediated phosphorylation at Thr169 perturbs mycobacterial guanylate kinase activity.

Guanylate kinase is an essential and conserved enzyme in nucleotide biosynthetic pathway that transfers phosphoryl group of ATP to GMP for yielding GDP. Here, we report the phosphorylation of guanylate kinase from Mycobacterium tuberculosis (mGmk) by eukaryotic-type Ser/Thr kinase, PknA. Mass spectrometric studies identified Thr101 and Thr169 as phosphorylatable residues in mGmk. To evaluate the significance of phosphorylation in these threonines, two point (T101A and T169A) and one double (T101A-T169A) mutants were generated. The kinase assay with these mutant proteins revealed the major contribution of Thr169 compared with Thr101 in the phosphorylation of mGmk. Kinetic analysis indicated that p-mGmk was deficient in its enzymatic activity compared with that of its un-phosphorylated counterpart. Surprisingly, its phosphoablated (T169A) as well as phosphomimic (T169E) variants exhibited decreased activity as was observed with p-mGmk. Structural analysis suggested that phosphorylation of Thr169 might affect its interaction with Arg166, which is crucial for the functioning of mGmk. In fact, the R166A and R166K mutant proteins displayed a drastic decrease in enzymatic activity compared with that of the wild-type mGmk. Molecular dynamics (MD) studies of mGmk revealed that upon phosphorylation of Thr169, the interactions of Arg165/Arg166 with Glu158, Asp121 and residues of the loop in GMP-binding domain are perturbed. Taken together, our results illuminate the mechanistic insights into phosphorylation-mediated modulation of the catalytic activity of mGmk.

Molecular dynamics studies unravel role of conserved residues responsible for movement of ions into active site of DHBPS.

3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) catalyzes the conversion of D-ribulose 5-phosphate (Ru5P) to L-3,4-dihydroxy-2-butanone-4-phosphate in the presence of Mg2+. Although crystal structures of DHBPS in complex with Ru5P and non-catalytic metal ions have been reported, structure with Ru5P along with Mg2+ is still elusive. Therefore, mechanistic role played by Mg2+ in the structure of DHBPS is poorly understood. In this study, molecular dynamics simulations of DHBPS-Ru5P complex along with Mg2+ have shown entry of Mg2+ from bulk solvent into active site. Presence of Mg2+ in active site has constrained conformations of Ru5P and has reduced flexibility of loop-2. Formation of hydrogen bonds among Thr-108 and residues - Gly-109, Val-110, Ser-111, and Asp-114 are found to be critical for entry of Mg2+ into active site. Subsequent in silico mutations of residues, Thr-108 and Asp-114 have substantiated the importance of these interactions. Loop-4 of one monomer is being proposed to act as a "lid" covering the active site of other monomer. Further, the conserved nature of residues taking part in the transfer of Mg2+ suggests the same mechanism being present in DHBPS of other microorganisms. Thus, this study provides insights into the functioning of DHBPS that can be used for the designing of inhibitors.

Molecular dynamics simulations show altered secondary structure of clawless in binary complex with DNA providing insights into aristaless-clawless-DNA ternary complex formation.

Aristaless (Al) and clawless (Cll) homeodomains that are involved in leg development in Drosophila melanogaster are known to bind cooperatively to 5'-(T/C)TAATTAA(T/A)(T/A)G-3' DNA sequence, but the mechanism of their binding to DNA is unknown. Molecular dynamics (MD) studies have been carried out on binary, ternary, and reconstructed protein-DNA complexes involving Al, Cll, and DNA along with binding free energy analysis of these complexes. Analysis of MD trajectories of Cll-3A01, binary complex reveals that C-terminal end of helixIII of Cll, unwind in the absence of Al and remains so in reconstructed ternary complex, Cll-3A01-Al. In addition, this change in secondary structure of Cll does not allow it to form protein-protein interactions with Al in the ternary reconstructed complex. However, secondary structure of Cll and its interactions are maintained in other reconstructed ternary complex, Al-3A01-Cll where Cll binds to Al-3A01, binary complex to form ternary complex. These interactions as observed during MD simulations compare well with those observed in ternary crystal structure. Thus, this study highlights the role of helixIII of Cll and protein-protein interactions while proposing likely mechanism of recognition in ternary complex, Al-Cll-DNA.

Management of complex femoral nonunion with monorail external fixator: A prospective study.

AIM: To evaluate 30 patients who underwent distraction osteogenesis with monorail external fixator for complex femoral nonunion. METHOD: Complex femoral nonunion includes infective non-union, gap nonunion, and limb-length discrepancy secondary to traumatic bone loss, which needs specialized treatment to ensure the functional integrity of femoral bone. 30 patients, including 28 male and 2 female (aged 22-62 years) patients, underwent surgical debridement followed by bone transport with monorail fixator. The lengthening index, radiographic consolidation index, functional status, bone healing, and various problems, obstacles, and complications encountered during the treatment were assessed. RESULTS: Patients underwent a mean of 2.2 (range 1-4) surgeries before presentation. The mean bone defect after surgical debridement was 5.83 cm (range 2-16 cm). The mean treatment duration was 204.7 days (range 113-543 days). The mean lengthening index was 13.06 days/cm with range from 12 to 16 days/cm. Mean maturation index was 23.51 days/cm with range from 17 to 45.5 days/cm. In our study, bone result was excellent in 17, good in 9, fair in 3, and poor in 1 patient. In our study functional outcome is excellent in 9 [30%], good in 14 [46.67%], fair in 5, and poor in 2 patients. In our study, we encountered 34 problems, 17 obstacles, and 8 complications. CONCLUSION: We concluded that monorail external fixator is an effective treatment option for complex nonunion femoral shaft fracture and its functional outcome is comparable with any other treatment options. Lack of complications and its effectiveness makes monorail external fixator the treatment of choice for complex nonunion femoral shaft.

Cosmetic arm lengthening with monorail fixator.

Upper limb length discrepancy is a rare occurrence. Humerus shortening may need specialized treatment to restore the functional and cosmetic status of upper limb. We report a case of humerus lengthening of 9 cm with a monorail external fixator and the result was observed during a 2-year follow-up. Humerus lengthening needs specialized focus as it is not only a cosmetic issue but also a functional demand. The monorail unilateral fixator is more functional and cosmetically acceptable, and thus becomes an effective treatment option.

PEPstrMOD: structure prediction of peptides containing natural, non-natural and modified residues.

BACKGROUND: In the past, many methods have been developed for peptide tertiary structure prediction but they are limited to peptides having natural amino acids. This study describes a method PEPstrMOD, which is an updated version of PEPstr, developed specifically for predicting the structure of peptides containing natural and non-natural/modified residues. RESULTS: PEPstrMOD integrates Forcefield_NCAA and Forcefield_PTM force field libraries to handle 147 non-natural residues and 32 types of post-translational modifications respectively by performing molecular dynamics using AMBER. AMBER was also used to handle other modifications like peptide cyclization, use of D-amino acids and capping of terminal residues. In addition, GROMACS was used to implement 210 non-natural side-chains in peptides using SwissSideChain force field library. We evaluated the performance of PEPstrMOD on three datasets generated from Protein Data Bank; i) ModPep dataset contains 501 non-natural peptides, ii) ModPep16, a subset of ModPep, and iii) CyclicPep contains 34 cyclic peptides. We achieved backbone Root Mean Square Deviation between the actual and predicted structure of peptides in the range of 3.81-4.05 Å. CONCLUSIONS: In summary, the method PEPstrMOD has been developed that predicts the structure of modified peptide from the sequence/structure given as input. We validated the PEPstrMOD application using a dataset of peptides having non-natural/modified residues. PEPstrMOD offers unique advantages that allow the users to predict the structures of peptides having i) natural residues, ii) non-naturally modified residues, iii) terminal modifications, iv) post-translational modifications, v) D-amino acids, and also allows extended simulation of predicted peptides. This will help the researchers to have prior structural information of modified peptides to further design the peptides for desired therapeutic property. PEPstrMOD is freely available at http://osddlinux.osdd.net/raghava/pepstrmod/.