Mapping enzymatic catalysis using the effective fragment molecular orbital method: towards all ab initio biochemistry

TY - JOUR

T1 - Mapping enzymatic catalysis using the effective fragment molecular orbital method

T2 - towards all ab initio biochemistry

AU - Svendsen, Casper Steinmann

AU - Fedorov, Dmitri G.

AU - Jensen, Jan Halborg

N1 - O.A.

PY - 2013/4/12

Y1 - 2013/4/12

N2 - We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We determine the reaction barrier of chorismate mutase to be 18.3±3.5 kcal mol-1 for MP2/cc-pVDZ and 19.3±3.6 for MP2/cc-pVTZ in an ONIOM approach using EFMO-RHF/6-31G(d) for the high and low layers, respectively.

AB - We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We determine the reaction barrier of chorismate mutase to be 18.3±3.5 kcal mol-1 for MP2/cc-pVDZ and 19.3±3.6 for MP2/cc-pVTZ in an ONIOM approach using EFMO-RHF/6-31G(d) for the high and low layers, respectively.

KW - Biocatalysis

KW - Biochemistry

KW - Chorismate Mutase

KW - Chorismic Acid

KW - Cyclohexanecarboxylic Acids

KW - Cyclohexenes

KW - Models, Molecular

KW - Thermodynamics

KW - Time Factors

U2 - 10.1371/journal.pone.0060602

DO - 10.1371/journal.pone.0060602

M3 - Journal article

C2 - 23593259

SN - 1932-6203

VL - 8

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

M1 - e60602

ER -