Vibrational entropy estimation can improve binding affinity prediction for non-obligatory protein complexes.

Predicting the binding affinity between protein monomers is of paramount importance for the understanding of thermodynamical and structural factors that guide the formation of a complex. Several numerical techniques have been developed for the calculation of binding affinities with different levels of accuracy. Approaches such as thermodynamic integration and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) methodologies which account for well defined physical interactions offer good accuracy but are computationally demanding. Methods based on the statistical analysis of experimental structures are much cheaper but good performances have only been obtained throughout consensus energy functions based on many different molecular descriptors. In this study we investigate the importance of the contribution to the binding free energy of the entropic term due to the fluctuations around the equilibrium structures. This term, which we estimated employing an elastic network model, is usually neglected in most statistical approaches. Our method crucially relies on a novel calibration procedure of the elastic network force constant. The residue mobility profile is fitted to the one obtained through a short all-atom molecular dynamics simulation on a subset of residues only. Our results show how the proper consideration of vibrational entropic contributions can improve the quality of the prediction on a set of non-obligatory protein complexes whose binding affinity is known.

Anthrax Lethal Factor Investigated by Molecular Simulations.

The anthrax disease is caused by the lethal toxin secreted by the bacterium Bacillus anthracis. The toxin is a protein aggregate which contains a Zn-based hydrolase called anthrax Lethal Factor (LF). In this work, we investigate the structure of its Michaelis complex with an optimized MAPKK-like substrate using several computational methods including density functional theory, molecular dynamics, and coarse grained techniques. Our calculations suggest that (i) the presence of second-shell ligands is crucial for tuning the structure, energetics, and protonation state of the metal binding site, as found in other Zn-based enzymes; (ii) the nucleophilic agent is a Zn-bound water molecule; (iii) substrate binding to the active site groove is mainly stabilized by van der Waals interactions; (iv) the bonds most likely involved in the substrate hydrolysis are only mildly polarized by the protein scaffold; and (v) part of helix α19, which is present in one solid state structure of LF (PDB: 1JKY ), assumes a coiled conformation.

The Standard Genetic Code and its relation to mutational pressure: robustness and equilibrium criteria

Under the assumption of even point mutation pressure on the DNA strand, rates for transitions from one amino acid into another were assessed. Nearly 25por ciento of all mutations were silent. About 48por ciento of the mutations from a given amino acid stream either into the same amino acid or into an amino acid of the same class. These results suggest a great stability of the Standard Genetic Code respect to mutation load. Concepts from chemical equilibrium theory are applicable into this case provided that mutation rate constants are given. It was obtained that unequal synonymic codon usage may lead to changes in the equilibrium concentrations. Data from real biological species showed that several amino acids are close to the respective equilibrium concentration. However in all the cases the concentration of leucine nearly doubled its equilibrium concentration, whereas for the stop command (Term) it was about 10 times lower. The overall distance from equilibrium for a set of species suggests that eukaryotes are closer to equilibrium than prokaryotes, and the HIV virus was closest to equilibrium among 15 species. We obtained that contemporary species are closer to the equilibrium than the Last Universal Common Ancestor (LUCA) was. Similarly, non-preserved regions in proteins are closer to equilibrium than the preserved ones. We suggest that this approach can be useful for exploring some aspects of biological evolution in the framework of Standard Genetic Code properties(AU)

Computación Biomolecular: algunos apuntes / Calculation Biomolecular: some notes

Se aborda el problema del desarrollo de sistemas computacionales basados en la aplicación de principios y soportes procedentes de la biología. En opinión de los autores, la investigación en la frontera de la biología y la física con las tecnologías de la información puede llevar al desarrollo de nuevos e importantes sistemas de información (algoritmos y software) y tecnologías de computación (hardware). La cuestión es qué y cómo podemos aprender (y entender) de los sistemas biológicos y físicos y cómo podemos adoptarlos y adaptarlos para desarrollar las tecnologías de la información del futuro. La computación biomolecular y la computación cuántica persiguen estos objetivos.El hecho de que diferentes tipos de tareas no resueltas hasta el presente mediante las tecnologías tradicionales encuentre su soluciónen el marco de la computación biomolecular puede considerarse como la mejor evidencia de las amplias perspectivas de este enfoque(AU)

La señal fotopletismográfica procesada con herramientas de análisis de serie de tiempo no lineal / The photoplethismographic signal processed with nonlinear time series analysis tools

Este trabajo aborda el análisis de las señales fotopletismográficas digitales (PPG) con herramientas no-lineales de serie de tiempo. Para esto se aplicaron las siguientes técnicas analíticas: I-Estimación polinomial de alto grado para la corrección de la línea base II-Análisis espectral mediante transformada rápida de Fourier III-Estimación de la dimensión fractal mediante el método propuesto por Higuchi para el dominio del tiempo IV-Estimación no paramétrica por núcleos para la reconstrucción de los atractores libres de ruido y de los componentes estocásticos de las señales. La señal PPG puede ser dividida en los tres componentes siguientes: 1. Una tendencia no-estacionaria, no-lineal dependiente del tiempo que se relaciona con la mayor parte de la no-estacionaridad de la señal PPG 2.Un componente no-lineal de ciclo límite determinístico invariante que corresponde a la generación de ondas pulsátiles que reflejan el punto más relevante de la señal PPG en los estudios clínicos 3.Un componente estocástico que sea, por lo menos, fractal parcialmente. Este componente soporta menos del 5 por ciento de la varianza de la señal corregida básica. La suma de la base (1) más los componentes estocásticos (3) puede explorar las propiedades fractales de la señal PPG original. Se considera que la separación de la señal PPG en tres componentes diferentes posibilita la obtención de nueva información, tanto para las investigaciones básicas, como para propósitos clínicos(AU)