MolDy: molecular dynamics simulation made easy.

MOTIVATION: Molecular dynamics (MD) is a computational experiment that is crucial for understanding the structure of biological macro and micro molecules, their folding, and the inter-molecular interactions. Accurate knowledge of these structural features is the cornerstone in drug development and elucidating macromolecules functions. The open-source GROMACS biomolecular MD simulation program is recognized as a reliable and frequently used simulation program for its precision. However, the user requires expertise, and scripting skills to carrying out MD simulations. RESULTS: We have developed an end-to-end interactive MD simulation application, MolDy for Gromacs. This front-end application provides a customizable user interface integrated with the Python and Perl-based logical backend connecting the Linux shell and Gromacs software. The tool performs analysis and provides the user with simulation trajectories and graphical representations of relevant biophysical parameters. The advantages of MolDy are (i) user-friendly, does not requiring the researcher to have prior knowledge of Linux; (ii) easy installation by a single command; (iii) freely available for academic research; (iv) can run with minimum configuration of operating systems; (v) has valid default prefilled parameters for beginners, and at the same time provides scope for modifications for expert users. AVAILABILITY AND IMPLEMENTATION: MolDy is available freely as compressed source code files with user manual for installation and operation on GitHub: https://github.com/AIBResearchMolDy/Moldyv01.git and on https://aibresearch.com/innovations.

iTRAQ proteomics of sentinel lymph nodes for identification of extracellular matrix proteins to flag metastasis in early breast cancer.

Patients with early breast cancer are affected by metastasis to axillary lymph nodes. Metastasis to these nodes is crucial for staging and quality of surgery. Sentinel Lymph Node Biopsy that is currently used to assess lymph node metastasis is not effective. This necessitates identification of biomarkers that can flag metastasis. Early stage breast cancer patients were recruited. Surgical resection of breast was followed by identification of sentinel lymph nodes. Fresh frozen section biopsy was used to assign metastatic and non-metastatic sentinel lymph nodes. Discovery phase included iTRAQ proteomics coupled with mass spectrometric analysis to identify differentially expressed proteins. Data is available via ProteomeXchange with identifier PXD027668. Validation was done by bioinformatic analysis and ELISA. There were 2398 unique protein groups and 109 differentially expressed proteins comparing metastatic and non-metastatic lymph nodes. Forty nine proteins were up-regulated, and sixty proteins that were down regulated in metastatic group. Bioinformatic analysis showed ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed up-regulation of ECM proteins in metastatic lymph nodes. ECM proteins have requisite parameters to be developed as a diagnostic tool to assess status of sentinel lymph nodes to guide surgical intervention in early breast cancer.

Proteomics of Sentinel Lymph Nodes in Early Breast Cancer for Identification of Thymidylate Synthase as a Potential Biomarker to Flag Metastasis: A Preliminary Study.

INTRODUCTION: Breast cancer is the second most common cancer in women across the world. Some of the patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and its diagnosis is crucial for the staging of cancer thereby dictating the type of surgical therapy. Therefore, the sentinel lymph node status provides the most relevant information to the surgeon and patient prognosis. The expanded utilization of breast conservation surgery has declined the morbidity associated with mastectomy and axillary lymph node surgery. Recent interest is, therefore, centered on techniques that allow accurate assessment of the sentinel lymph node metastasis. A current procedure such as sentinel lymph node biopsy (SLNB) that is used to assess axillary lymph node metastasis is neither specific nor sensitive, and besides, it is time-consuming. OBJECTIVE: To compare the protein profiles between metastatic and non-metastatic lymph nodes to identify a biomarker that can flag lymph node metastasis. MATERIALS AND METHODS: Women with early breast cancer were screened using mammography imaging and recruited to the study. Surgical resection was done to remove the breast tissue, and sentinel lymph node was identified using fluorescein and methylene blue tracer. Lymph node was sliced, and one set was sent for histopathology, which was considered the gold standard to assess the metastatic status of the lymph node. One set of slices was taken for proteomic experiments. Proteins were labelled with fluorescent cyanine tags and were subjected to difference gel electrophoresis experiment. Differentially expressed spots that had at least a twofold relative ratio and consistent pattern across three sets of biological replicate experiments were marked. Gel spots were trypsin digested and identified on mass spectrometry machine. Validation study was done by Western blot experiment on the same set of samples. RESULTS: Thymidylate synthase has a twofold higher expression in the metastatic sentinel lymph nodes as compared to non-metastatic lymph nodes in early breast cancer patients. CONCLUSION: Differential in gel expression proteomics is an ideal platform for the identification of potential protein biomarker candidates that can differentiate metastatic from non-metastatic lymph nodes in early breast cancer. The identification of thymidylate synthase offers a scope to develop an on-table diagnostic kit to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical management of axillary lymph nodes in early breast cancer.