Solutions to the computational protein folding problem

Abstract

Collaborative efforts combining computational biology, structural biology and statistical physics expertise provide a solution to the computational protein folding problem. Genomic sequences contain rich evolutionary information about functional constraints on macromolecules such as proteins. This information can be efficiently mined to detect evolutionary couplings between residues in proteins and address the long-standing challenge to compute protein and RNA three-dimensional structures from sequences alone. Substantial progress on the evolutionary couplings approach, since the initial attempts in 1994, has become possible because of the explosive growth in available sequences and the application of global statistical methods, such as maximum entropy distillation of correlated mutation patterns. In addition to proteins and RNA 3D structure, this powerful analysis of covariation helps identify functional residues involved in ligand binding, complex formation and conformational changes. We expect computation of evolutionary covariation patterns to help elucidate the full spectrum of protein and RNA structures, their functional interactions and evolutionary dynamics. Collaboration between the Sander and Marks (Harvard Medical School) groups, as well as initially with Martin Weigt, Andrea Pagnani and Riccardo Zecchina at Politecnico di Torino. Use the http://evfold.org server to compute EVcouplings and to predict 3D structure for large sequence families. Ref: Protein 3D Structure from high-throughput sequencing http://bit.ly/tob48p. Ref: 3D RNA and Functional Interactions from Evolutionary Couplings http://bit.ly/3D_RNA. Support or Funding Information NIH R01, MSKCC internal, DFCI internal. Fold your own protein on EVfold.org - needs about 1000 homologs in the protein family. Marks and Sander labs, Harvard Medical School. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.