RESUMO
X-ray diffraction crystallography is the primary technique to determine the three-dimensional structures of biomolecules. Although a robust method, X-ray crystallography is not able to access the dynamical behavior of macromolecules. To do so, we have to carry out molecular dynamics simulations taking as an initial system the three-dimensional structure obtained from experimental techniques or generated using homology modeling. In this chapter, we describe in detail a tutorial to carry out molecular dynamics simulations using the program NAMD2. We chose as a molecular system to simulate the structure of human cyclin-dependent kinase 2.
Assuntos
Simulação de Dinâmica Molecular , Software , Trifosfato de Adenosina/química , Algoritmos , Cristalografia por Raios X , Quinase 2 Dependente de Ciclina/química , Humanos , Conformação Proteica , Eletricidade Estática , Interface Usuário-ComputadorRESUMO
AutoDock is one of the most popular receptor-ligand docking simulation programs. It was first released in the early 1990s and is in continuous development and adapted to specific protein targets. AutoDock has been applied to a wide range of biological systems. It has been used not only for protein-ligand docking simulation but also for the prediction of binding affinity with good correlation with experimental binding affinity for several protein systems. The latest version makes use of a semi-empirical force field to evaluate protein-ligand binding affinity and for selecting the lowest energy pose in docking simulation. AutoDock4.2.6 has an arsenal of four search algorithms to carry out docking simulation including simulated annealing, genetic algorithm, and Lamarckian algorithm. In this chapter, we describe a tutorial about how to perform docking with AutoDock4. We focus our simulations on the protein target cyclin-dependent kinase 2.
Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Software , Trifosfato de Adenosina/química , Quinase 2 Dependente de Ciclina/química , Desenho de Fármacos , Ligação de Hidrogênio , Ligantes , Conformação Molecular , Ligação Proteica , Proteínas/química , Interface Usuário-ComputadorRESUMO
Molegro Virtual Docker is a protein-ligand docking simulation program that allows us to carry out docking simulations in a fully integrated computational package. MVD has been successfully applied to hundreds of different proteins, with docking performance similar to other docking programs such as AutoDock4 and AutoDock Vina. The program MVD has four search algorithms and four native scoring functions. Considering that we may have water molecules or not in the docking simulations, we have a total of 32 docking protocols. The integration of the programs SAnDReS ( https://github.com/azevedolab/sandres ) and MVD opens the possibility to carry out a detailed statistical analysis of docking results, which adds to the native capabilities of the program MVD. In this chapter, we describe a tutorial to carry out docking simulations with MVD and how to perform a statistical analysis of the docking results with the program SAnDReS. To illustrate the integration of both programs, we describe the redocking simulation focused the cyclin-dependent kinase 2 in complex with a competitive inhibitor.
Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Software , Sítios de Ligação , Quinase 2 Dependente de Ciclina/química , Desenho de Fármacos , Humanos , Ligantes , Ligação Proteica , Proteínas/química , Interface Usuário-ComputadorRESUMO
GEMDOCK is a protein-ligand docking software that makes use of an elegant biologically inspired computational methodology based on the differential evolution algorithm. As any docking program, GEMDOCK has two major features to predict the binding of a small-molecule ligand to the binding site of a protein target: the search algorithm and the scoring function to evaluate the generated poses. The GEMDOCK scoring function uses a piecewise potential energy function integrated into the differential evolutionary algorithm. GEMDOCK has been applied to a wide range of protein systems with docking accuracy similar to other docking programs such as Molegro Virtual Docker, AutoDock4, and AutoDock Vina. In this chapter, we explain how to carry out protein-ligand docking simulations with GEMDOCK. We focus this tutorial on the protein target cyclin-dependent kinase 2.
Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas/química , Software , Trifosfato de Adenosina/química , Quinase 2 Dependente de Ciclina/química , Bases de Dados de Proteínas , Desenho de Fármacos , Ligantes , Interface Usuário-ComputadorRESUMO
Protein-ligand docking simulation is central in drug design and development. Therefore, the development of web servers intended to docking simulations is of pivotal importance. SwissDock is a web server dedicated to carrying out protein-ligand docking simulation intuitively and elegantly. SwissDock is based on the protein-ligand docking program EADock DSS and has a simple and integrated interface. The SwissDock allows the user to upload structure files for a protein and a ligand, and returns the results by e-mail. To facilitate the upload of the protein and ligand files, we can prepare these input files using the program UCSF Chimera. In this chapter, we describe how to use UCSF Chimera and SwissDock to perform protein-ligand docking simulations. To illustrate the process, we describe the molecular docking of the competitive inhibitor roscovitine against the structure of human cyclin-dependent kinase 2.
Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Software , Algoritmos , Quinase 2 Dependente de Ciclina/química , Desenho de Fármacos , Humanos , Ligantes , Proteínas/química , Interface Usuário-Computador , NavegadorRESUMO
Molecular docking is the major computational technique employed in the early stages of computer-aided drug discovery. The availability of free software to carry out docking simulations of protein-ligand systems has allowed for an increasing number of studies using this technique. Among the available free docking programs, we discuss the use of ArgusLab ( http://www.arguslab.com/arguslab.com/ArgusLab.html ) for protein-ligand docking simulation. This easy-to-use computational tool makes use of a genetic algorithm as a search algorithm and a fast scoring function that allows users with minimal experience in the simulations of protein-ligand simulations to carry out docking simulations. In this chapter, we present a detailed tutorial to perform docking simulations using ArgusLab.