Name: Nisha Paudel
Barrier to resources: No access to either institute or national resources.
Expected scientific output: Publication and collaboration.
Title: Dinucleotide abundance in all life
Abstract: Background: Dinucleotide is two adjacent nucleotides in a DNA separated by a single phosphate group. From the four nitrogen bases, (4*4) 16 dinucleotides can be derived, which are ApA, ApT, ApG, ApC, TpA, TpT, TpG, TpC, GpA, GpT, GpG, GpC, CpA, CpT, CpG and CpC From the statistical point of view, the ratio of all dinucleotides is expected to be 1 as one dinucleotide is found in every 16 dinucleotides. But it can be observed that only a few dinucleotides tend to follow this. This has caused the distinct signature of dinucleotide and its difference among different species (Gentles, A. J. (2001). This may be due to DNA replication and repair mechanisms and biases in DNA modification processes like base-step stacking energies and DNA conformational tendencies, context-dependent mutation, and DNA methylation patterns (Karlin 1998).
Rationale: This study is conducted to know which dinucleotides are over-and under-represented in the various phyla of organisms from archaea, bacteria, protozoa, fungi, plants, invertebrates, and vertebrates, why their abundance is different in different genomic regions.
Results: Violin plot (below) displaying the distribution of dinucleotides human promoter 1kbp upstream and downstream from the TSS region, The X-axis shows all the 16 dinucleotides and the Y-axis shows the ratio count per sequence length.
Name: Victor Hugo Vargas Bermudez
Position: Postgraduate student (last year)
Barrier to resources: The host cluster hasn’t received maintenance since 2021.
Expected scientific output: Thesis chapter
Title: Computational modelling of the tissue factor – factor VIIa complex dynamics involved in thrombosis.
Abstract: Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels. CVDs are the number one cause of death worldwide (17.9 million in 2019) (WHO, 2022). Venous thrombosis is an affection associated with CVDs, and it consists of blood clot formation that could be delocalized and move to the lungs and heart, causing heart attacks and strokes in four out of five CVD deaths. Venous thrombosis is treated with anticoagulant drugs directed to the cascade coagulation (CC) proteins as a primary target. Protein Factor VIIa (fVIIa) interacts with the protein Tissue factor (TF) at the CC’s starting point. High concentrations of fVIIa protein circulating in the blood could trigger thrombosis when it’s docked to its target, the TF protein. The primary goal of anticoagulant drugs is to reduce the activity of different CC proteins. Vitamin K antagonists and heparins are the main class of drugs used as a treatment for thrombosis. The aim of the present work is to clarify the molecular mechanisms involved in the interaction between TF-FVIIa proteins to gain information for a further searching of therapeutics molecules with minimal secondary effects. The methods involved are: (i) MD simulations of a system (TF-FVIIa complex) consisting of up to 160,000 atoms and a simulation time of 100 nanoseconds; (ii) virtual screening of more than 130,000 molecules on three different sites of the FVIIa protein; and (iii) MD simulations of FVIIa protein with some of the best-scored ligands resulting from the virtual screening. For MD simulations we will be using AmberTools, Amber, and Gromacs software. Virtual screening will be performed using AutoDock. The analysis of the results will be obtained using Python built-in packages.
Name: Shamrat Kumar Paul
Position: MSc student
Barrier to resources: Till now we are up to the structure prediction and 100ns of molecular dynamics simulation of our protein of interest (166 aa long) using GROMACS and OPLS-aa force field, taking nearly one and a half months to simulation 100ns timespan. All these studies were accomplished using an i5 personal CPU which is owned by one of my friends and not an institutional facility. We have the plan to extend my MS thesis study to the rest of two or three protein structures having a similar length to our current studied protein but the way of the accomplishment of the rest of our plan is uncertain due to the limited access of HPC/Cluster Computing Workstation/Servers.
Expected scientific output: MSc Thesis
Title: Molecular dynamics simulation study of proteins overexpressed in experimental autoimmune encephalomyelitis mice.
Abstract: Molecular dynamics Simulation Study of a Protein that is overexpressed in Experimental Autoimmune Encephalomyelitis Mice where we are focused to determine the comparative structure of the protein through the swiss-model and subsequent RMSD, RMSF and Rg study. Later on, we have the plan to elucidate the active site as well as the binding site about the interaction with drug-like molecules as ligand.