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Improving the CHARMM36m force field for arginine-phosphate interactions by Jiyeon Min; Madolyn Britt; Sergei I. Sukharev; Bernard R. Brooks; Jeffery B. Klauda is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Improving the CHARMM36m force field for arginine-phosphate interactions about?

The Kristen Rat Sarcoma (KRAS) protein, encoded by the KRAS gene, is a signal transducer that plays a crucial role in regulating cell proliferation. KRAS mutations have been known to cause lung, colorectal, and pancreatic cancers. Previously, KRAS was considered an "undruggable" target. However, with a better understanding of the protein's biology paired with advanced new technologies, the FDA approved the first KRAS inhibitor (sotorasib) for lung cancer patients with the KRASG12C mutation in 2021, expressing the recent interest of targeted drugs for KRAS. Oncogenic KRAS requires activation by the guanine nucleotide exchange factor (GEF) Son of Sevenless 1 (SOS1). The goal of this study is to develop novel pan-KRAS inhibitors by targeting the KRAS-SOS1 interactions through computational modeling. To start, we applied Gaussian accelerated molecular dynamics (GaMD) simulation, an advanced conformational sampling method, to collect the nature of the KRAS protein motion in solution. Then, the clustering analysis method was used to assemble KRAS conformational structures into ten groups. Finally, virtual screening and docking simulations are performed using the ChemBridge molecule datab

Who reads Improving the CHARMM36m force field for arginine-phosphate interactions?

Author

Jiyeon Min; Madolyn Britt; Sergei I. Sukharev; Bernard R. Brooks; Jeffery B. Klauda

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)