Molecular dynamics-driven drug discovery: leaping forward with confidence

被引:264
作者
Ganesan, Aravindhan [1 ]
Coote, Michelle L. [2 ]
Barakat, Khaled [1 ]
机构
[1] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB, Canada
[2] Australian Natl Univ, ARC Ctr Excellence Elect Sci, Res Sch Chem, Canberra, ACT 2601, Australia
关键词
FREE-ENERGY CALCULATIONS; PROTEIN-STRUCTURE REFINEMENT; BINDING FREE-ENERGIES; REACTIVE FORCE-FIELD; EXPLICIT SOLVENT; NONNUCLEOSIDE INHIBITORS; CONFORMATIONAL-ANALYSIS; COMPUTATIONAL ANALYSIS; MULTIPLE INHIBITORS; STRUCTURAL DYNAMICS;
D O I
10.1016/j.drudis.2016.11.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Given the significant time and financial costs of developing a commercial drug, it remains important to constantly reform the drug discovery pipeline with novel technologies that can narrow the candidates down to the most promising lead compounds for clinical testing. The past decade has witnessed tremendous growth in computational capabilities that enable in silico approaches to expedite drug discovery processes. Molecular dynamics (MD) has become a particularly important tool in drug design and discovery. From classical MD methods to more sophisticated hybrid classical/quantum mechanical (QM) approaches, MD simulations are now able to offer extraordinary insights into ligand-receptor interactions. In this review, we discuss how the applications of MD approaches are significantly transforming current drug discovery and development efforts.
引用
收藏
页码:249 / 269
页数:21
相关论文
共 205 条
[41]  
2-N
[42]  
David CC, 2014, METHODS MOL BIOL, V1084, P193, DOI 10.1007/978-1-62703-658-0_11
[43]   Role of Molecular Dynamics and Related Methods in Drug Discovery [J].
De Vivo, Marco ;
Masetti, Matteo ;
Bottegoni, Giovanni ;
Cavalli, Andrea .
JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (09) :4035-4061
[44]   How the flexibility of human histone deacetylases influences ligand binding: an overview [J].
Deschamps, Nathalie ;
Simoes-Pires, Claudia Avello ;
Carrupt, Pierre-Alain ;
Nurisso, Alessandra .
DRUG DISCOVERY TODAY, 2015, 20 (06) :736-742
[45]   A novel lipid binding site formed by the MAP kinase insert in p38α [J].
Diskin, Ron ;
Engelberg, David ;
Livnah, Oded .
JOURNAL OF MOLECULAR BIOLOGY, 2008, 375 (01) :70-79
[46]   Synthesis and biological assessment of novel 2-thiazolylhydrazones and computational analysis of their recognition by monoamine oxidase B [J].
Distinto, Simona ;
Yanez, Matilde ;
Alcaro, Stefano ;
Cardia, M. Cristina ;
Gaspari, Marco ;
Sanna, M. Luisa ;
Meleddu, Rita ;
Ortuso, Francesco ;
Kirchmair, Johannes ;
Markt, Patrick ;
Bolasco, Adriana ;
Wolber, Gerhard ;
Secci, Daniela ;
Maccioni, Elias .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 48 :284-295
[47]   Constant pH Molecular Dynamics in Explicit Solvent with λ-Dynamics [J].
Donnini, Serena ;
Tegeler, Florian ;
Groenhof, Gerrit ;
Grubmueller, Helmut .
JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2011, 7 (06) :1962-1978
[48]   Three-dimensional protein structure prediction: Methods and computational strategies [J].
Dorn, Marcio ;
Barbachan e Silva, Mariel ;
Buriol, Luciana S. ;
Lamb, Luis C. .
COMPUTATIONAL BIOLOGY AND CHEMISTRY, 2014, 53 :251-276
[49]   Molecular dynamics simulations and drug discovery [J].
Durrant, Jacob D. ;
McCammon, J. Andrew .
BMC BIOLOGY, 2011, 9
[50]   On the inhibition of histone deacetylase 8 [J].
Estiu, Guillermina ;
West, Nathan ;
Mazitschek, Ralph ;
Greenberg, Edward ;
Bradner, James E. ;
Wiest, Olaf .
BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (11) :4103-4110