M. S. Tomás

Development of a kinetic model for elemental sulfur and sulfate formation from the autotrophic sulfide oxidation using respirometric techniques

A kinetic model for the elemental sulfur and sulfate production from the autotrophic sulfide oxidation has been proposed. It is based on two kinetic equations able to describe the simultaneous microbial consumption of oxygen and sulfide (OUR and SUR) as a function of a particular sulfide-oxidizing microorganism or its physiological state, these can be characterized by the assessment of their kinetic constants. The respirometric technique allowed to estimate the dynamic experimental OUR and SUR profiles, which were used to calibrate the kinetic model. The ratio OUR/SUR was proposed to predict the sulfide oxidation extent and then the fate of sulfide to elemental sulfur and sulfate.

Some remarkable lines of triangles in real normed spaces and characterizations of inner product structures

SummaryIn this work we consider the heights and the bisectrices of a triangle in a real normed space. Using well-known formulas which can be generalized to real normed spaces we obtain a collection of new characterizations of inner product spaces.

Insight into the Binding of DFG-out Allosteric Inhibitors to B-Raf Kinase Using Molecular Dynamics and Free Energy Calculations

B-Raf mutations are identified in 40-50% of patients with melanoma and among them, the substitution of valine for glutamic acid at position 600 ((V600E)B-Raf) is the most frequent. Treatment of these patients with B-Raf inhibitors has been associated with a clear clinical benefit. Unfortunately, multiple resistance mechanisms have been identified and new potent and selective inhibitors are currently needed. In this work, five different type II inhibitors, which bind (V600E)B-Raf in its DFG-out conformation, have been studied using molecular dynamics, free energy calculations and energy decomposition analysis. The ranking of calculated MM-PB/GBSA binding affinities is in good agreement with the experimentally measured ones. The per-residue decomposition of ΔGbinding, within the MM-GBSA approach, has been used to identify the key residues governing the allosteric binding of the studied compounds to the (V600E)B-Raf protein kinase. Results indicate that although van der Waals interactions are key determinants for binding, hydrogen bonds also play an important role. This work also provides a better structural understanding of the binding of DFG-out inhibitors to (V600E)B-Raf, which can be used in a further step for rational design of a new class of B-Raf potent inhibitors.

On some functional equations arising in computer graphics

Summary. Motivated by the analysis of some graphic-geometric aspects of some functions used in computer graphics for modelizing real objects, we study some functional equations which, under some assumptions, characterize these functions.

A multistep docking and scoring protocol for congeneric series: Implementation on kinase DFG-out type II inhibitors

AIM Rescoring of docking-binding poses can significantly improve molecular docking results. Our aim was to evaluate postprocessing docking protocols in order to determine the most suitable methodology for the study of the binding of congeneric compounds to protein kinases. MATERIALS & METHODS Diverse ligand-receptor poses generated after docking were submitted to different relaxation protocols. The Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area approach was applied for the evaluation of the binding affinity of complexes obtained. The performance of various Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area methodologies was compared. RESULTS The inclusion of a postprocessing protocol after docking enhances the quality of the results, although the best methodology is system dependent. CONCLUSION An examination of the interactions established has allowed us to suggest useful modifications for the design of new type II inhibitors.