相关论文: Molecular Dynamics Studies on HIV-1 Protease: Drug…

An exactly solvable model based on the topology of a protein native state is applied to identify bottlenecks and key-sites for the folding of HIV-1 Protease. The predicted sites are found to correlate well with clinical data on resistance…

Predicting how protein mutations affect drug binding remains a major challenge, particularly when the mutations are distal from the binding site. In this study, we introduce a coupled simulation workflow that combines long-time-scale…

Being the HIV-1 Protease (HIV-1-PR) an essential enzyme in the viral life cycle, its inhibition can control AIDS. The folding of single domain proteins, like each of the monomers forming the HIV-1-PR homodimer, is controlled by local…

One of the main problems of drug design is that of optimizing the drug--target interaction. In the case in which the target is a viral protein displaying a high mutation rate, a second problem arises, namely the eventual development of…

Learning how proteins fold will hardly have any impact in the way conventional -- active site centered -- drugs are designed. On the other hand, this knowledge is proving instrumental in defining a new paradigm for the identification of…

These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient…

Being HIV-1-PR an essential enzyme in the viral life cycle, its inhibition can control AIDS. Because the folding of single domain proteins, like HIV-1-PR is controlled by local elementary structures (LES, folding units stabilized by…

A central question is how the conformational changes of proteins affect their function and the inhibition of this function by drug molecules. Many enzymes change from an open to a closed conformation upon binding of substrate or inhibitor…

We introduce a simple theoretical approach for an equilibrium study of proteins with known native state structures. We test our approach with results on well-studied globular proteins, Chymotrypsin Inhibitor (2ci2), Barnase and the alpha…

The evolution of drug resistance in HIV occurs by the fixation of specific, well-known, drug-resistance mutations, but the underlying population genetic processes are not well understood. By analyzing within-patient longitudinal sequence…

Drug resistance remains a major problem for the treatment of HIV. Resistance can occur due to mutations that were present before treatment starts or due to mutations that occur during treatment. The relative importance of these two sources…

Motivation: HIV is difficult to treat because its virus mutates at a high rate and mutated viruses easily develop resistance to existing drugs. If the relationships between mutations and drug resistances can be determined from historical…

$\textbf{Background:}$ High mutability of HIV is the driving force of antiretroviral drug resistance, which represents a medical care challenge. $\textbf{Method and Model Equation:}$ To detect the mutability of each gene in the HIV-1…

Conventional drugs work, as a rule, by inhibiting the enzymatic activity of specific proteins, capping their active site. In this paper we present a model of non- conventional drug design based on the inhibiting effects small peptides…

The relevance of various residue positions for the stability and the folding characteristics of the prion protein are investigated by using molecular dynamics simulations of models exploiting the topology of the native state. Highly…

Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics and tumors resistant to anti-cancer drugs. We use a statistical physics model to study the evolution of a population of malignant…

The folding dynamics of small single-domain proteins is a current focus of simulations and experiments. Many of these proteins are 'two-state folders', i.e. proteins that fold rather directly from the denatured state to the native state,…

Structure-based virtual screening aims to identify high-affinity ligands by estimating binding free energies between proteins and small molecules. However, the conformational flexibility of both proteins and ligands challenges conventional…

Human immunodeficiency virus (HIV) evolves with extraordinary rapidity. However, its evolution is constrained by interactions between mutations in its fitness landscape. Here we show that an Ising model describing these interactions,…

We present a rigidity analysis on a large number of X-ray crystal structures of the enzyme HIV-1 protease using the 'pebble game' algorithm of the software FIRST. We find that although the rigidity profile remains similar across a…