更多资讯

The relevance of histone acetylation/deacetylation in regulating decompaction/compaction of chromatin and, consequently, in regulating gene expression, has been described for many physiological and pathological biological processes, including normal and altered e ...

DNA methylation is an epigenetic form of gene regulation that is universally important throughout the life course, especially during in utero and postnatal development. DNA methylation aids in cell cycle regulation and cellular differentiation processes. Previous studies have ...

The non-structural 3 protease is an essential flaviviral enzyme and therefore one of the most promising targets for drug development against West Nile virus infections. In this chapter, we discuss in detail the computational methods used in the previous two docking campaigns which lead to t ...

Cannabinoids represent a promising class of compounds for developing novel therapeutic agents. Since the isolation and identification of the major psychoactive component Δ9-THC in Cannabis sativa in the 1960s, numerous analogues of the classical plant cannabinoids have been sy ...

Computational simulation of pandemic diseases provides important insight into many disease features that may benefit public health. This is especially true for the influenza virus, a continuing global pandemic threat. Molecular or atomic-level investigation of influenza has p ...

We present an example-based description of virtual screening (VS) techniques used to identify new regulators of the Akt phosphatase PHLPP (PH domain Leucine repeat Protein Phosphatase). This enzyme opposes the effects of two kinases, Akt and PKC, which play a major role in cell growth and survi ...

HIV-1 protease is a major drug target for AIDS therapy. With the appearance of drug-resistant HIV-1 protease variants, understanding the mechanism of drug resistance becomes critical for rational drug design. Computational methods can provide more details about inhibitor-prote ...

Molecular dynamics (MD) is a way to computationally simulate the movement of particles and it is widely used to provide a dynamic perspective on biomolecules. Nowadays, the ever-growing computer power and the improvement in methodology further strengthen the role of MD in drug discovery. In ...

The method of accelerated molecular dynamics (aMD) has been shown to increase the rate of phase-space sampling in biomolecular simulations. In this chapter, we discuss the theory behind aMD and describe the implementation of two versions: dual-boost and selective aMD. Each method has its pr ...

Large-scale conformational transitions represent both a challenge and an opportunity for computational drug design. Exploring the conformational space of a druggable target with sufficient detail is computationally demanding. However, if it were possible to fully account for ...

The one-step perturbation approach offers an efficient means to estimate free energy differences. It may be applied to estimate solvation free energies, conformational preferences or relative free energies of binding of series of compounds to a common receptor. Applicability of the m ...

The Independent-Trajectory Thermodynamic Integration (IT-TI) approach for free energy calculation with distributed computing is described. IT-TI utilizes diverse conformational sampling obtained from multiple, independent simulations to obtain more reliable free ...

Free energy calculations are increasingly of interest for computing biophysical properties of novel small molecules of interest in drug design, such as protein–ligand binding affinities and small molecule partition coefficients. However, these calculations are also notori ...

Among the many applications of molecular modeling, drug design is probably the one with the highest demands on the accuracy of the underlying structures. During lead optimization, the position of every atom in the binding site should ideally be known with high precision to identify those chem ...

Water molecules at the binding interface of biomolecular complexes or water molecules displaced from hydrophobic cavities have lately been recognized as important modulators of binding affinity. One approach to computing the contribution of these water molecules to solvation ...

The effects of solvation on molecular recognition are investigated from different perspectives, ranging from methods to analyse explicit solvent dynamical behaviour at the protein surface to methods for the implicit treatment of solvent effects associated with the conformat ...

Water molecules are active components in, literally, every biochemical event, forming hydrogen bonds, filling cavities, and mediating interactions with other (bio)molecules. Therefore, solvent drastically affects the kinetics and thermodynamics of numerous cellular ev ...

Conformational entropy is an important component of the change in free energy upon binding of a ligand to its target protein. As a consequence, development of computational techniques for reliable estimation of conformational entropies is currently receiving an increased level of at ...

A broad range of computational methods exist for the estimation of ligand–protein binding affinities. In this chapter we will provide a guide to the linear interaction energy (LIE) method for binding free energy calculations, focusing on the drug design problem. The method is implemented in ...

The solvated interaction energy (SIE) is an end-point, physics-based scoring function for predicting ligand-binding affinities. It supplements the force-field interaction energy with the desolvation cost of binding. Parameters such as the solute dielectric constant, Born ra ...