Computational Drug Discovery and Design

3.5 Umbrella Sampling (US) Protocol for Unbinding Process 3.5.1 Bias and Parameter Set In this methodology, the main idea is to ...

construct the PMF (Fig.4). US protocol has become a routine method for the study of events involving nonequilibrium states, such ...

The US calculation consists to simulate several windows along the chosen restrained variableζ, in order to correctly sample and ...

With the AMBER suite, Umbrella Sampling calculation gen- erates a dump file, in which all the values of the restrained variable ...

energy variation of the dissociation of the complex. The obtained profile in our case is shown on Fig.6. The estimated energetic ...

MD simulations. It can be further used to populate the conforma- tional ensemble of a multiconformational docking. The RC nonde- ...

during the simulation through classical analyzes such as the root mean square deviation, the root mean square fluctuation, and r ...

covariance matrix (only with a correlation matrix in the case of a normalized PCA). In addition to the 2D principal component p ...

Copeland RA (2011) Conformational adapta- tion in drug-target interactions and residence time. Future Med Chem 3:1491–1501. htt ...

Torrie GM, Valleau JP (1977) Nonphysical sampling distributions in Monte Carlo free- energy estimation: umbrella sampling. J Co ...

Chapter 21 AGGRESCAN3D: Toward the Prediction of the Aggregation Propensities of Protein Structures Jordi Pujols, Samuel Pen ̃a- ...

of the fragile equilibrium between protein solubility and aggrega- tion by energetically favoring the native conformations of ta ...

in the folded state of amino acids that are originally distant in the sequence. In folded conformations, these potentially dange ...

to solvent, approximated as the relative surface area (RSA) using the Lee and Richards method implemented in the Naccess server ...

hindrance between amino acid side chains and suboptimal rotamer configurations of residues in close vicinity [37]. Then, the ser ...

3.2 Run Options In the lower panel of the submission box named ‘options’the user can name the project and introduce an e-mail ad ...

submission, this will open a new interactive window entitled “which residue to mutate?”where the amino acids from the 3D structu ...

Fig. 3Output and evaluation. Ensemble of A3D output results obtained after a Dynamic run using the PDB code 2FEJ:A, no mutation, ...

The user is able to obtain global scores accounting for the overall protein propensity as well as for each specific amino acid ( ...

3.5 Evaluating the A3D Output The evaluation of A3D predictions and the subsequent identifica- tion of relevant APRs would benef ...