Predicting Reactive Cysteines with Implicit-Solvent-Based Continuous Constant pH Molecular Dynamics in Amber.

ABSTRACT: Cysteines existing in the deprotonated thiolate form or having a tendency to become deprotonated are important players in enzymatic and cellular redox functions and frequently exploited in covalent drug design; however, most computational studies assume cysteines as protonated. Thus, developing an efficient tool that can make accurate and reliable predictions of cysteine protonation states is timely needed. We recently implemented a generalized Born (GB) based continuous constant pH molecular dynamics (CpHMD) method in Amber for protein pK_a calculations on CPUs and GPUs. Here we benchmark the performance of GB-CpHMD for predictions of cysteine pK_a's and reactivities using a data set of 24 proteins with both down- and upshifted cysteine pK_a

SUBMITTER: Harris RC 

PROVIDER: S-EPMC7772776 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature