The Possible Origin of the Biochemical Function of Proteins and its Implications for the Origin of Life

Skolnick, Jeffrey

Title:

The Possible Origin of the Biochemical Function of Proteins and its Implications for the Origin of Life

dc.contributor.author	Skolnick, Jeffrey
dc.contributor.corporatename	Georgia Institute of Technology. Institute for Bioengineering and Bioscience	en_US
dc.contributor.corporatename	Georgia Institute of Technology. School of Biological Sciences	en_US
dc.contributor.corporatename	Georgia Institute of Technology. Center for the Study of Systems Biology	en_US
dc.date.accessioned	2020-04-02T18:57:31Z
dc.date.available	2020-04-02T18:57:31Z
dc.date.issued	2020-03-10
dc.description	Presented on March 10, 2020 at 9:00 a.m. in the Parker H. Petit Institute for Bioengineering and Bioscience, Room 1128, Georgia Tech.	en_US
dc.description	Parker H. Petit Institute for Bioengineering and Bioscience (IBB) Breakfast Club Seminar Series.	en_US
dc.description	Jeffrey Skolnick, Professor, Mary and Maisie Gibson Chair; Director, Center for the Study of Systems Biology; and Georgia Research Alliance Eminent Scholar in Computational Systems Biology, Georgia Tech.	en_US
dc.description	Runtime: 38:23 minutes	en_US
dc.description.abstract	Living systems have chiral molecules,; e.g., native proteins almost entirely contain L-amino acids. How protein homochirality emerged from a background of equal numbers of L and D amino acids is among many questions about life’s origin. The origin of homochirality and its implications are explored in computer simulations examining the stability, structural and functional properties of an artificial library of compact proteins containing 1:1, termed demi-chiral, 3:1 and 1:3 ratios of D:L and purely L or D amino acids generated without functional selection. Demi-chiral proteins have shorter secondary structures, fewer internal hydrogen bonds, and are less stable than homochiral proteins. Selection for hydrogen bonding yields a preponderance of L or D amino acids. Demi-chiral proteins have native global folds, including similarity to early ribosomal proteins, similar small molecule ligand binding pocket geometries, and many constellations of L-chiral amino acids with a 1.0 Å RMSD to native enzyme active sites. For a representative subset containing 550 active site geometries matching 457 (2) four (three) E.C digits, native active site amino acids were generated at random for 472/550 cases. This increases to 548/550 cases when similar residues are allowed. The most frequently generated sequences correspond to ancient enzymatic functions, e.g., glycolysis, replication, and nucleotide biosynthesis. Surprisingly, even without selection, demi-chiral proteins possess the requisite marginal biochemical function and structure of modern proteins, but were thermodynamically less stable. If demi-chiral proteins were present, they could engage in early metabolism, which created the feedback loop for transcription and cell formation.	en_US
dc.format.extent	38:23 minutes
dc.identifier.uri	http://hdl.handle.net/1853/62541
dc.language.iso	en_US	en_US
dc.publisher	Georgia Institute of Technology	en_US
dc.relation.ispartofseries	Petit Institute Breakfast Club Seminar Series
dc.subject	Ancient metabolism	en_US
dc.subject	Inherent biochemical function	en_US
dc.subject	Origin of chirality	en_US
dc.title	The Possible Origin of the Biochemical Function of Proteins and its Implications for the Origin of Life	en_US
dc.type	Moving Image
dc.type.genre	Lecture
dspace.entity.type	Publication
local.contributor.author	Skolnick, Jeffrey
local.contributor.corporatename	Parker H. Petit Institute for Bioengineering and Bioscience
local.relation.ispartofseries	Petit Institute Breakfast Club Seminar Series
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relation.isOrgUnitOfPublication	d978f252-ad5a-4fe6-a735-21050b2d760e
relation.isSeriesOfPublication	037a6ee9-c6f0-4f20-abb8-e229d98f6754