Molecular Dynamics Simulations in Protein-Protein Docking.

Concerted interactions between all the cell components form the basis of biological processes. Protein-protein interactions (PPIs) constitute a tremendous part of this interaction network. Deeper insight into PPIs can help us better understand numerous diseases and lead to the development of new diagnostic and therapeutic strategies. PPI interfaces, until recently, were considered undruggable. However, it is now believed that the interfaces contain "hot spots," which could be targeted by small molecules. Such a strategy would require high-quality structural data of PPIs, which are difficult to obtain experimentally. Therefore, in silico modeling can complement or be an alternative to in vitro approaches. There are several computational methods for analyzing the structural data of the binding partners and modeling of the protein-protein dimer/oligomer structure. The major problem with in silico structure prediction of protein assemblies is obtaining sufficient sampling of protein dynamics. One of the methods that can take protein flexibility and the effects of the environment into account is Molecular Dynamics (MD). While sampling of the whole protein-protein association process with plain MD would be computationally expensive, there are several strategies to harness the method to PPI studies while maintaining reasonable use of resources. This chapter reviews known applications of MD in the PPI investigation workflows.

Role of N-terminus in function and dynamics of sirtuin 7: an in silico study.

The sirtuin family comprises seven NAD+-dependent histone deacetylases named SIRT1 to SIRT7. The least investigated SIRT7 is currently considered as a promising therapeutic target for cardiovascular diseases, diabetes and different types of cancer. So far, its structure was not experimentally resolved, except of a fragment of its N-terminus. The aim of this study was to create in silico model of SIRT7 containing its core together with N-terminus, which is known to affect the enzyme's catalytic activity and to find pockets that could be targeted by structure-based virtual screening. Homology model of SIRT7 was prepared using X-ray structures of other sirtuins and a resolved fragment of the N-terminus of SIRT7 as templates. All atom-unbiased molecular dynamics simulations were performed. It was found that N-terminus of SIRT7 remains in spatial proximity of the catalytic core for considerable fraction of time, and therefore, it may affect its catalytic activity by helping the enzyme to hold the substrate peptide. It may also participate in holding and release of the cofactor. Preferred orientations of NAD+ and acetyl-lysine inside SIRT7 were found, with all components forming a stable complex. Molecular dynamics provided an ensemble of conformations that will be targeted with virtual screening. Reliable in silico structure of SIRT7 will be a useful tool in searching for its inhibitors, which can be potential drugs in cancer treatment.Communicated by Ramaswamy H. Sarma.

Vaccination among Polish university students. Knowledge, beliefs and anti-vaccination attitudes.

Anti-vaccination movement has existed as long as the vaccines themselves, but its mode of action and social influences evolved over time. Such attitude with no doubt has negative impact on vaccination rates and eradication of infectious diseases. In this study, we used an online survey to examine vaccination attitudes of Polish university students of various degree and specialties. A total of 1,386 questionnaires were completed, among them 617 from students attending medical schools and 769 from students of non-medical schools. Up to 95.24% (N = 1320) of the study subjects, among them 98.70% and 92.46% of students of medical and non-medical specialties, respectively, declared willingness to vaccinate their children. 47.19% (N = 654) of participants have a contact with anti-vaccination propaganda at least once in a lifetimes. 42.64% (N = 591) of respondents were aware of the existence of anti-vaccination movements; 45.35% (N = 414) of participants, including 306 (51.52%) and 108 (33.86%) students of medical and non-medical disciplines, respectively, considered such movements as a negative phenomenon. Vaccination attitudes of students from medical and non-medical universities differed considerably. Vaccination knowledge and awareness among the students from non-medical universities were rather poor, markedly lower than in the students of medical disciplines. Nevertheless, irrespective of their major, Polish students have considerable knowledge gaps with regards to vaccination and need additional education in this matter.