Allosteric pockets and dynamic residue network hubs of falcipain 2 in mutations including those linked to artemisinin resistance.

ABSTRACT: Continually emerging resistant strains of malarial parasites to current drugs present challenges. Understanding the underlying resistance mechanisms, especially those linked to allostery is, thus, highly crucial for drug design. This forms the main concern of the paper through a case study of falcipain 2 (FP-2) and its mutations, some of which are linked to artemisinin (ART) drug resistance. Here, we applied a variety of in silico approaches and tools that we developed recently, together with existing computational tools. This included novel essential dynamics and dynamic residue network (DRN) analysis algorithms. We identified six pockets demonstrating dynamic differences in the presence of some mutations. We observed striking allosteric effects in two mutant proteins. In the prese

SUBMITTER: Okeke CJ 

PROVIDER: S-EPMC8545671 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature