Improved contact prediction in proteins: Using pseudolikelihoods to infer Potts models

Spatially proximate amino acids in a protein tend to coevolve. A protein's three-dimensional (3D) structure hence leaves an echo of correlations in the evolutionary record. Reverse engineering 3D structures from such correlations is an open problem in structural biology, pursued with increasing vigor as more and more protein sequences continue to fill the data banks. Within this task lies a statistical inference problem, rooted in the following: correlation between two sites in a protein sequence can arise from firsthand interaction but can also be network-propagated via intermediate sites; observed correlation is not enough to guarantee proximity. To separate direct from indirect interactions is an instance…