gbart's Aldrich [3 articles]

Abstract

MOTIVATION: The constituent amino acids of a protein work together to define its structure and to facilitate its function. Their interdependence should be apparent in the evolutionary record of each protein family: positions in the sequence of a protein family that are intimately associated in space or in function should co-vary in evolution. A recent approach by Ranganathan and colleagues proposes to look at subsets of a protein family, selected for their sequence at one position, to see how this affects ...

Abstract

10.1074/jbc.M402560200 The inherent complexity of thermodynamic coupling in proteins presents a major challenge in understanding and engineering protein function. Recent work has argued that the study of proteins can be simplified by the use of correlated mutations in the evolutionary record to locate a small subset of thermodynamically coupled residues that participate in functionally important, evolutionarily conserved energetic pathways. To test this hypothesis, we examined the predictions of correlated mutation algorithms for a number of proteins for which coupling between residues ...

Abstract

It has long been argued that algorithms that find correlated mutations in multiple sequence alignments can be used to find structurally or functionally important residues in proteins. We examined the properties of four different methods for detecting these correlated mutations. On both simple, artificial alignments and real alignments from the Pfam database, we found a surprising lack of agreement between the four correlated mutation methods. We argue that these differences are caused in part by differing sensitivities to background conservation. Correlated ...