title: The interface of protein structure, protein biophysics, and molecular evolution.
abstract: Abstract The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction.
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, Wyoming 82071, USA. liberles@uwyo.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Liberles
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Teichmann
authors.forename: Ivet
authors.initials: I
authors.lastname: Bahar
authors.forename: Ugo
authors.initials: U
authors.lastname: Bastolla
authors.forename: Jesse
authors.initials: J
authors.lastname: Bloom
authors.forename: Erich
authors.initials: E
authors.lastname: Bornberg-Bauer
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Colwell
authors.forename: A P Jason
authors.initials: AP
authors.lastname: de Koning
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
authors.forename: Julian
authors.initials: J
authors.lastname: Echave
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
authors.forename: Dietlind L
authors.initials: DL
authors.lastname: Gerloff
authors.forename: Richard A
authors.initials: RA
authors.lastname: Goldstein
authors.forename: Johan A
authors.initials: JA
authors.lastname: Grahnen
authors.forename: Mark T
authors.initials: MT
authors.lastname: Holder
authors.forename: Clemens
authors.initials: C
authors.lastname: Lakner
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lartillot
authors.forename: Simon C
authors.initials: SC
authors.lastname: Lovell
authors.forename: Gavin
authors.initials: G
authors.lastname: Naylor
authors.forename: Tina
authors.initials: T
authors.lastname: Perica
authors.forename: David D
authors.initials: DD
authors.lastname: Pollock
authors.forename: Tal
authors.initials: T
authors.lastname: Pupko
authors.forename: Lynne
authors.initials: L
authors.lastname: Regan
authors.forename: Andrew
authors.initials: A
authors.lastname: Roger
authors.forename: Nimrod
authors.initials: N
authors.lastname: Rubinstein
authors.forename: Eugene
authors.initials: E
authors.lastname: Shakhnovich
authors.forename: Kimmen
authors.initials: K
authors.lastname: Sjölander
authors.forename: Shamil
authors.initials: S
authors.lastname: Sunyaev
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Teufel
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Thorne
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Thornton
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Weinreich
authors.forename: Simon
authors.initials: S
authors.lastname: Whelan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D011506:Proteins; D012333:RNA, Messenger