Tuesday, August 25th, 2020

Resistance Mechanisms of E. coli on the Inhibition of DHFR

Antibiotic resistance is a common health problem that requires urgent and creative solutions. According to the Centers for Disease Control and Prevention, USA, globally more than 150,000 deaths per year occurs due to antibiotic resistance. Thus, current medical practices seek a thorough understanding of the purpose of developing proper approaches to attack this problem. Dihydrofolate reductase (DHFR) is an enzyme that catalyzes the hydride transfer from the cofactor NADPH to 7,8-dihydrofolate (DHF) to facilitate the formation of 5,6,7,8-tetrahydrofolate (THF). THF is a critical carbon carrier in the biosynthesis of nucleotides which makes DHFR an important player on cell growth and proliferation. Trimethoprim (antibiotic) and methotrexate (antineoplastic agent) are known inhibitors of DHFR which are used in therapeutics. Trimethoprim was synthesized in 1962 and is the last original antibiotic produced; all other antibiotics produced are some variation of older antibiotics. Trimethoprim inhibits the function of DHFR by competitively binding the enzyme, displacing dihydrofolate. We are trying to understand the physical rationale behind the resistant DHFR binding mechanisms and selectivity of the enzyme between DHF and Trimethoprim. In pursuit of this aim, we use atomistic level Molecular Dynamics simulations and utilize the Free Energy Perturbation Method to understand energetic effects of resistance, to trace the roots of catalytic efficiency and selectivity towards the substrate.

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Tuesday, August 25th, 2020

Beta2 Adrenergic

Two different communication mechanism of proteins are investigated. Mechanical domain communication is investigated by remodelling usually omitted part of ╬▓2-Ar intracellular loop 3 and its unbinding energy from inactive to the active state is estimated. Allosteric communications within the protein are dwelled on via correlation matrices of intra-communications between residues

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Wednesday, August 29th, 2018

Research Scope

Proteins are nanomachines of life. They regulate the processes from the most simple to complex in order to pertain life. When we think life on cell scale, everything sits on an energy landscape with many routes coming in and going out from one minimum to another. The question nags my mind is how the genetic information of past and future communicates with the present state of the cell through physical conditions. To understand this, I am currently working on understanding how a cell changing the dynamics of a protein after exposure to chemical pressure such as an antibiotic.

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