Bridging solvent molecules mediate RNase A - Ligand binding.

ABSTRACT: Due to its high catalytic activity and readily available supply, ribonuclease A (RNase A) has become a pivotal enzyme in the history of protein science. Moreover, this great interest has carried over to computational chemistry and molecular dynamics, where RNase A has become a model system for various types of studies, all the while being an important drug design target in its own right. Here, we present a detailed molecular dynamics study of RNase-ligand binding involving 22 compounds, spanning nearly five orders of magnitude in affinity, and totaling 8.8 μs of sampling with the standard Amber parameters and an additional 8.8 μs of sampling with a modified potential. We show that short-lived, solvent-mediated bridging interactions are crucial to RNase-ligand binding. We characterize the b

SUBMITTER: Ivanov SM 

PROVIDER: S-EPMC6808499 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature