Computational design of enzyme-ligand binding using a combined energy function and deterministic sequence optimization algorithm
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| 005 | 20210128100658.0 | ||
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| 008 | 210128e20150801xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.1007/s00894-015-2742-x |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00894-015-2742-x | ||
| 245 | 0 | 0 | |a Computational design of enzyme-ligand binding using a combined energy function and deterministic sequence optimization algorithm |h [Elektronische Daten] |c [Ye Tian, Xiaoqiang Huang, Yushan Zhu] |
| 520 | 3 | |a Enzyme amino-acid sequences at ligand-binding interfaces are evolutionarily optimized for reactions, and the natural conformation of an enzyme-ligand complex must have a low free energy relative to alternative conformations in native-like or non-native sequences. Based on this assumption, a combined energy function was developed for enzyme design and then evaluated by recapitulating native enzyme sequences at ligand-binding interfaces for 10 enzyme-ligand complexes. In this energy function, the electrostatic interaction between polar or charged atoms at buried interfaces is described by an explicitly orientation-dependent hydrogen-bonding potential and a pairwise-decomposable generalized Born model based on the general side chain in the protein design framework. The energy function is augmented with a pairwise surface-area based hydrophobic contribution for nonpolar atom burial. Using this function, on average, 78% of the amino acids at ligand-binding sites were predicted correctly in the minimum-energy sequences, whereas 84% were predicted correctly in the most-similar sequences, which were selected from the top 20 sequences for each enzyme-ligand complex. Hydrogen bonds at the enzyme-ligand binding interfaces in the 10 complexes were usually recovered with the correct geometries. The binding energies calculated using the combined energy function helped to discriminate the active sequences from a pool of alternative sequences that were generated by repeatedly solving a series of mixed-integer linear programming problems for sequence selection with increasing integer cuts. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Computational enzyme design |2 nationallicence | |
| 690 | 7 | |a Protein-ligand interaction |2 nationallicence | |
| 690 | 7 | |a Protein design |2 nationallicence | |
| 690 | 7 | |a Energy function |2 nationallicence | |
| 690 | 7 | |a Global optimization |2 nationallicence | |
| 700 | 1 | |a Tian |D Ye |u Department of Chemical Engineering, Tsinghua University, 100084, Beijing, People's Republic of China |4 aut | |
| 700 | 1 | |a Huang |D Xiaoqiang |u Department of Chemical Engineering, Tsinghua University, 100084, Beijing, People's Republic of China |4 aut | |
| 700 | 1 | |a Zhu |D Yushan |u Department of Chemical Engineering, Tsinghua University, 100084, Beijing, People's Republic of China |4 aut | |
| 773 | 0 | |t Journal of Molecular Modeling |d Springer Berlin Heidelberg |g 21/8(2015-08-01), 1-14 |x 1610-2940 |q 21:8<1 |1 2015 |2 21 |o 894 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00894-015-2742-x |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00894-015-2742-x |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Tian |D Ye |u Department of Chemical Engineering, Tsinghua University, 100084, Beijing, People's Republic of China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Huang |D Xiaoqiang |u Department of Chemical Engineering, Tsinghua University, 100084, Beijing, People's Republic of China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Zhu |D Yushan |u Department of Chemical Engineering, Tsinghua University, 100084, Beijing, People's Republic of China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Modeling |d Springer Berlin Heidelberg |g 21/8(2015-08-01), 1-14 |x 1610-2940 |q 21:8<1 |1 2015 |2 21 |o 894 | ||