Apr 9, 2020

Discovering loop conformational flexibility in T4 lysozyme mutants through Artificial Intelligence aided Molecular Dynamics

BioRxiv : the Preprint Server for Biology
Z. SmithPratyush Tiwary

Abstract

Proteins sample a large variety of conformations distinct from their crystal structure. These structures, their thermodynamic propensities, and the pathways for moving between them contain a wealth of information about protein function that is hidden from a purely structural perspective. Molecular dynamics simulations can uncover these higher energy states but often at a prohibitively high computational cost. Here we apply our recent statistical mechanics and artificial intelligence based all-atom molecular dynamics framework for enhanced sampling of protein loops in three mutants of the protein T4 lysozyme. We are able to rank these three mutants according to the stability of their excited state and accurately recover the thermodynamic stability found through experiment. By an analysis of the optimized reaction coordinates, we also obtain crucial insight into why these specific but small perturbations in sequence space lead to tremendous variations in conformational flexibility. Our framework thus allows accurate comparison of loop conformation populations without the extensive computational resources previously required to conduct such a study, and should be directly applicable to a range of macromolecules including proteins,...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Genetic Programming
Amino Acids, I.V. solution additive
Analysis
Open Reading Frames
Point Mutation
Frameshift Mutation Function
Genetic Code
Landscapes
Antifibrinolytic amino acids

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.