Role of the biomolecular energy gap in protein design, structure, and evolution

Sarel J. Fleishman; David Baker

doi:10.1016/j.cell.2012.03.016

Role of the biomolecular energy gap in protein design, structure, and evolution

Sarel J. Fleishman
, David Baker

Department of Biomolecular Sciences

Weizmann Institute of Science

Research output: Contribution to journal › Review article › peer-review

Abstract

The folding of natural biopolymers into unique three-dimensional structures that determine their function is remarkable considering the vast number of alternative states and requires a large gap in the energy of the functional state compared to the many alternatives. This Perspective explores the implications of this energy gap for computing the structures of naturally occurring biopolymers, designing proteins with new structures and functions, and optimally integrating experiment and computation in these endeavors. Possible parallels between the generation of functional molecules in computational design and natural evolution are highlighted.

Original language	English
Pages (from-to)	262-273
Number of pages	12
Journal	Cell
Volume	149
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2012.03.016
State	Published - 13 Apr 2012

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2012.03.016

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@article{33efd133e2b64caa9bb6181c79c8258c,

title = "Role of the biomolecular energy gap in protein design, structure, and evolution",

abstract = "The folding of natural biopolymers into unique three-dimensional structures that determine their function is remarkable considering the vast number of alternative states and requires a large gap in the energy of the functional state compared to the many alternatives. This Perspective explores the implications of this energy gap for computing the structures of naturally occurring biopolymers, designing proteins with new structures and functions, and optimally integrating experiment and computation in these endeavors. Possible parallels between the generation of functional molecules in computational design and natural evolution are highlighted.",

author = "Fleishman, \{Sarel J.\} and David Baker",

note = "Geffen Trust; Yeda-Sela Center for Basic Research; National Institutes of Health; Defense Advanced Research Program Agency; Defense Threat Reduction Agency; Howard Hughes Medical InstituteThe authors thank Yibing Shan, David E. Shaw, Vladimir Yarov-Yarovoy, Mike Tyka, Oliver Lange, Rhiju Das, and Ingemar Andre for providing the data used to produce Figure 2 and Ingemar Andre, Gira Bhabha, Rhiju Das, Sagar Khare, Olga Khersonsky, Tanja Kortemme, Eva-Maria Strauch, and Dan S Tawfik for critical reading. S.J.F. is supported by a grant from the Geffen Trust, the Yeda-Sela Center for Basic Research, a donation from Sam Switzer and Family, and the Human Frontier Science Program. Research in the Baker lab was supported by grants from the National Institutes of Health, the Defense Advanced Research Program Agency, the Defense Threat Reduction Agency, and the Howard Hughes Medical Institute.",

year = "2012",

month = apr,

day = "13",

doi = "10.1016/j.cell.2012.03.016",

language = "English",

volume = "149",

pages = "262--273",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "2",

}

TY - JOUR

T1 - Role of the biomolecular energy gap in protein design, structure, and evolution

AU - Fleishman, Sarel J.

AU - Baker, David

N1 - Geffen Trust; Yeda-Sela Center for Basic Research; National Institutes of Health; Defense Advanced Research Program Agency; Defense Threat Reduction Agency; Howard Hughes Medical InstituteThe authors thank Yibing Shan, David E. Shaw, Vladimir Yarov-Yarovoy, Mike Tyka, Oliver Lange, Rhiju Das, and Ingemar Andre for providing the data used to produce Figure 2 and Ingemar Andre, Gira Bhabha, Rhiju Das, Sagar Khare, Olga Khersonsky, Tanja Kortemme, Eva-Maria Strauch, and Dan S Tawfik for critical reading. S.J.F. is supported by a grant from the Geffen Trust, the Yeda-Sela Center for Basic Research, a donation from Sam Switzer and Family, and the Human Frontier Science Program. Research in the Baker lab was supported by grants from the National Institutes of Health, the Defense Advanced Research Program Agency, the Defense Threat Reduction Agency, and the Howard Hughes Medical Institute.

PY - 2012/4/13

Y1 - 2012/4/13

N2 - The folding of natural biopolymers into unique three-dimensional structures that determine their function is remarkable considering the vast number of alternative states and requires a large gap in the energy of the functional state compared to the many alternatives. This Perspective explores the implications of this energy gap for computing the structures of naturally occurring biopolymers, designing proteins with new structures and functions, and optimally integrating experiment and computation in these endeavors. Possible parallels between the generation of functional molecules in computational design and natural evolution are highlighted.

AB - The folding of natural biopolymers into unique three-dimensional structures that determine their function is remarkable considering the vast number of alternative states and requires a large gap in the energy of the functional state compared to the many alternatives. This Perspective explores the implications of this energy gap for computing the structures of naturally occurring biopolymers, designing proteins with new structures and functions, and optimally integrating experiment and computation in these endeavors. Possible parallels between the generation of functional molecules in computational design and natural evolution are highlighted.

UR - https://www.scopus.com/pages/publications/84859765617

U2 - 10.1016/j.cell.2012.03.016

DO - 10.1016/j.cell.2012.03.016

M3 - Review article

SN - 0092-8674

VL - 149

SP - 262

EP - 273

JO - Cell

JF - Cell

IS - 2

ER -

Role of the biomolecular energy gap in protein design, structure, and evolution

Abstract

ASJC Scopus subject areas

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