title: Analysis of side-chain orientations in homologous proteins.
abstract: The side-chain conformations of topologically equivalent residues in seven pairs of proteins ranging in sequence homology from 16% to 60% are compared. Both identical and mutated residues are included. For proteins with greater than 40% homology, it is found that at least 80% of the side-chain orientations of identical residues and 75% or more of the mutated residues in each pair of proteins have matching gamma atom dihedral angles (+/- 40 degrees); the comparison is not based strictly on chi 1 angles. Further, if a match is obtained at the gamma position, there is a high probability of matching for the delta atom(s) of the side-chain. For proteins with less than 25% homology the percentages are somewhat lower. Trends observed for conservative substitutions are essentially the same as those noted for mutated residues in general. Side-chain accessibility does not affect the probability of matches of identical residues; however, less accessible pairs of mutated residues have 10 to 20% higher matching probabilities than do exposed residues. Mismatches can frequently be related to large B-factors, certain types of amino acid substitutions, or the appearance of multiple minima on the side-chain potential energy surfaces and are most likely to occur for certain small residues (Ser, Thr, Val). Analysis of all the results makes possible the formulation of a set of rules for side-chain positioning in the modeling of homologous proteins.
authors.affiliation: Molecular and Cellular Research Laboratory, Massachusetts General Hospital, Boston.
authors.forename: N L
authors.initials: NL
authors.lastname: Summers
authors.forename: W D
authors.initials: WD
authors.lastname: Carlson
authors.forename: M
authors.initials: M
authors.lastname: Karplus
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002918:Chymotrypsin; D010450:Endopeptidases; D004902:Erythrocruorins; D006420:Hemeproteins; D006454:Hemoglobins; D006801:Humans; D007874:Leghemoglobin; D008954:Models, Biological; D009113:Muramidase; D009154:Mutation; D009211:Myoglobin; D011487:Protein Conformation; D014357:Trypsin
chemical_list: D004902:Erythrocruorins; D006420:Hemeproteins; D006454:Hemoglobins; D007874:Leghemoglobin; D009211:Myoglobin; D009113:Muramidase; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; C022325:aspartic proteinase A; D016282:Aspartic Acid Endopeptidases; C042466:Endothia aspartic proteinase; C035794:rhizopuspepsin