東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Computational Modeling of (De)-Solva...

Yang, Ying.

FindBook

Google Book

Amazon

博客來

Computational Modeling of (De)-Solvation Effects and Protein Flexibility in Protein-Ligand Binding Using Molecular Dynamics Simulations.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Computational Modeling of (De)-Solvation Effects and Protein Flexibility in Protein-Ligand Binding Using Molecular Dynamics Simulations./
作者:	Yang, Ying.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	177 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-01, Section: B.
Contained By:	Dissertations Abstracts International81-01B.
標題:	Computational chemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10792169
ISBN:	9781085560702

Computational Modeling of (De)-Solvation Effects and Protein Flexibility in Protein-Ligand Binding Using Molecular Dynamics Simulations.
Yang, Ying.

Computational Modeling of (De)-Solvation Effects and Protein Flexibility in Protein-Ligand Binding Using Molecular Dynamics Simulations. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 177 p.

Source: Dissertations Abstracts International, Volume: 81-01, Section: B.

Thesis (Ph.D.)--Purdue University, 2018.

This item is not available from ProQuest Dissertations & Theses.

Water is a crucial participant in virtually all cellular functions. Evidently, water molecules in the binding site contribute significantly to the strength of intermolecular interactions in the aqueous phase by mediating protein-ligand interactions, solvating and de-solvating both ligand and protein upon protein-ligand dissociation and association. Recently many published studies use water distributions in the binding site to retrospectively explain and rationalize unexpected trends in structure-activity relationships (SAR). However, traditional approaches cannot quantitatively predict the thermodynamic properties of water molecules in the binding sites and its associated contribution to the binding free energy of a ligand.We have developed and validated a computational method named WATsite to exploit high-resolution solvation maps and thermodynamic profiles to elucidate the water molecules' potential contribution to protein-ligand and protein-protein binding. We have also demonstrated the utility of the computational method WATsite to help direct medicinal chemistry efforts by using explicit water de-solvation.In addition, protein conformational change is typically involved in the ligand-binding process which may completely change the position and thermodynamic properties of the water molecules in the binding site before or upon ligand binding. We have shown the interplay between protein flexibility and solvent reorganization, and we provide a quantitative estimation of the influence of protein flexibility on de- solvation free energy and, therefore, protein-ligand binding.Different ligands binding to the same target protein can induce different conformational adaptations. In order to apply WATsite to an ensemble of different protein conformations, a more efficient implementation of WATsite based on GPU-acceleration and system truncation has been developed. Lastly, by extending the simulation protocol from pure water to mixed water-organic probes simulations, accurate modeling of halogen atom-protein interactions has been achieved.

ISBN: 9781085560702Subjects--Topical Terms:

3350019
Computational chemistry.
Subjects--Index Terms:

De-solvation Free Energy

Computational Modeling of (De)-Solvation Effects and Protein Flexibility in Protein-Ligand Binding Using Molecular Dynamics Simulations.
LDR:03400nmm a2200397 4500 001 2272209
005 20201105105958.5
008 220629s2018 ||||||||||||||||| ||eng d
020 $a 9781085560702
035 $a (MiAaPQ)AAI10792169
035 $a AAI10792169
040 $a MiAaPQ $c MiAaPQ
100 1 $a Yang, Ying. $3 1927734
245 1 0 $a Computational Modeling of (De)-Solvation Effects and Protein Flexibility in Protein-Ligand Binding Using Molecular Dynamics Simulations.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2018
300 $a 177 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-01, Section: B.
500 $a Advisor: Lill, Markus A.
502 $a Thesis (Ph.D.)--Purdue University, 2018.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be sold to any third party vendors.
520 $a Water is a crucial participant in virtually all cellular functions. Evidently, water molecules in the binding site contribute significantly to the strength of intermolecular interactions in the aqueous phase by mediating protein-ligand interactions, solvating and de-solvating both ligand and protein upon protein-ligand dissociation and association. Recently many published studies use water distributions in the binding site to retrospectively explain and rationalize unexpected trends in structure-activity relationships (SAR). However, traditional approaches cannot quantitatively predict the thermodynamic properties of water molecules in the binding sites and its associated contribution to the binding free energy of a ligand.We have developed and validated a computational method named WATsite to exploit high-resolution solvation maps and thermodynamic profiles to elucidate the water molecules' potential contribution to protein-ligand and protein-protein binding. We have also demonstrated the utility of the computational method WATsite to help direct medicinal chemistry efforts by using explicit water de-solvation.In addition, protein conformational change is typically involved in the ligand-binding process which may completely change the position and thermodynamic properties of the water molecules in the binding site before or upon ligand binding. We have shown the interplay between protein flexibility and solvent reorganization, and we provide a quantitative estimation of the influence of protein flexibility on de- solvation free energy and, therefore, protein-ligand binding.Different ligands binding to the same target protein can induce different conformational adaptations. In order to apply WATsite to an ensemble of different protein conformations, a more efficient implementation of WATsite based on GPU-acceleration and system truncation has been developed. Lastly, by extending the simulation protocol from pure water to mixed water-organic probes simulations, accurate modeling of halogen atom-protein interactions has been achieved.
590 $a School code: 0183.
650 4 $a Computational chemistry. $3 3350019
650 4 $a Biophysics. $3 518360
650 4 $a Bioinformatics. $3 553671
653 $a De-solvation Free Energy
653 $a Halogen-bonding
653 $a Hydration Site
653 $a Molecular Dynamics
653 $a Protein Flexibility
653 $a WATsite
690 $a 0219
690 $a 0786
690 $a 0715
710 2 $a Purdue University. $b Medicinal Chemistry and Molecular Pharmacology. $3 1285856
773 0 $t Dissertations Abstracts International $g 81-01B.
790 $a 0183
791 $a Ph.D.
792 $a 2018
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10792169