changes in lysozyme flexibility upon mutation are frequent, large and long-ranged溶菌酶变化的灵活性在变异频繁,大型和远程.pdfVIP

Changes in Lysozyme Flexibility upon Mutation Are Frequent, Large and Long-Ranged 1 2 1 Deeptak Verma , Donald J. Jacobs *, Dennis R. Livesay * 1 Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina, United States of America, 2 Department of Physics and Optical Science, University of North Carolina at Charlotte, Charlotte, North Carolina, United States of America Abstract We investigate changes in human c-type lysozyme flexibility upon mutation via a Distance Constraint Model, which gives a statistical mechanical treatment of network rigidity. Specifically, two dynamical metrics are tracked. Changes in flexibility index quantify differences within backbone flexibility, whereas changes in the cooperativity correlation quantify differences within pairwise mechanical couplings. Regardless of metric, the same general conclusions are drawn. That is, small structural perturbations introduced by single point mutations have a frequent and pronounced affect on lysozyme flexibility that can extend over long distances. Specifically, an appreciable change occurs in backbone flexibility for 48% of the residues, and a change in cooperativity occurs in 42% of residue pairs. The average distance from mutation to a site with a change in ˚ flexibility is 17–20 A. Interestingly, the frequency and scale of the changes within single point mutant structures are generally larger than those observed in the hen egg white lysozyme (HEWL) ortholog, which shares 61% sequence identity with human lysozyme. For example, point mutations often lead to substantial flexibility increases within the b-subdomain, which is consistent with experimental result