Recent Advances on Computational Proteomics

In this work we report the recent progresses that have been achieved by our group in the last half decade on the field of computational proteomics. Specifically, we discuss the application of Molecular Dynamics Simulations and Electronic Structure Calculations in drug design, in the clarification of the structural and dynamic properties of proteins and enzymes and in the understanding of the catalytic and inhibition mechanism of cancer-related enzymes. A set of examples illustrate the concepts and help to introduce the reader into this important and fast moving field.

HIV Treatment Planning on a case-by-CASE Basis

This study presents a mathematical modeling approach to the planning of HIV therapies on an individual basis. The model replicates clinical data from typical-progressors to AIDS for all stages of the disease with good agreement. Clinical data from rapid-progressors and long-term non-progressors is also matched by estimation of immune system parameters only. The ability of the model to reproduce these phenomena validates the formulation, a fact which is exploited in the investigation of effective therapies. The therapy investigation suggests that, unlike continuous therapy, structured treatment interruptions (STIs) are able to control the increase in both the drug-sensitive and drug-resistant virus population and, hence, prevent the ultimate progression from HIV to AIDS. The optimization results further suggest that even patients characterised by the same progression type can respond very differently to the same treatment and that the latter should be designed on a case-by-case basis. Such a methodology is presented here.

Molecular Dynamics and Circular Dichroism Studies on Aurein 1.2 and Retro Analog

Aurein 1.2 is a 13-residue amphipathic peptide with antibacterial and anticancer activity. Aurein1.2 and its retro analog were synthesized to study the activity of the peptides in relation to their structure. The antibacterial test result showed the retro-analog is inactive. The secondary structural analysis by CD spectra indicated that both of the peptides at TFE/Water adopt alpha-helical conformation. MD simulation was performed on aurein 1.2 and retro-analog in water and TFE in order to analyse the factors that are involved in the activity difference between retro and the native peptide. The simulation results are discussed and validated in the light of experimental data from the CD experiment. Both of the peptides showed a relatively similar pattern for their hydrophobicity, hydrophilicity, solvent accessible surfaces, and solvent accessible hydrophobic surfaces. However, they showed different in directions of dipole moment of peptides. Also, Our results further indicate that the reversion of the amino acid sequence affects flexibility .The data also showed that factors causing structural rigidity may decrease the activity. Consequently, our finding suggests that in the case of sequence-reversed peptide strategy, one has to pay attention to the role of amino acid sequence order in making flexibility and role of dipole moment direction in peptide activity. KeywordsAntimicrobial peptides, retro, molecular dynamic, circular dichroism.

Application the Statistical Conditional Entropy Function for Definition of Cause-and-Effect Relations during Primary Soil Formation

Within the framework of a method of the information theory it is offered statistics and probabilistic model for definition of cause-and-effect relations in the coupled multicomponent subsystems. The quantitative parameter which is defined through conditional and unconditional entropy functions is introduced. The method is applied to the analysis of the experimental data on dynamics of change of the chemical elements composition of plants organs (roots, reproductive organs, leafs and stems). Experiment is directed on studying of temporal processes of primary soil formation and their connection with redistribution dynamics of chemical elements in plant organs. This statistics and probabilistic model allows also quantitatively and unambiguously to specify the directions of the information streams on plant organs.

Cloning and Over Expression of an Aspergillus niger XP Phytase Gene (phyA) in Pichia pastoris

A. niger XP isolated from Vietnam produces very low amount of acidic phytase with optimal pH at 2.5 and 5.5. The phytase production of this strain was successfully improved through gene cloning and expression. A 1.4 - kb DNA fragment containing the coding region of the phyA gene was amplified by PCR and inserted into the expression vector pPICZαA with a signal peptide α- factor, under the control of AOX1 promoter. The recombined plasmid was transformed into the host strain P. pastoris KM71H and X33 by electroporation. Both host strains could efficiently express and secret phytase. The multicopy strains were screened for over expression of phytase. All the selected multicopy strains of P. pastoris X33 were examined for phytase activity, the maximum phytase yield of 1329 IU/ml was obtained after 4 days of incubation in medium BMM. The recombinant protein with MW of 97.4 KW showed to be the only one protein secreted in the culture broth. Multicopy transformant P. pastoris X33 supposed to be potential candidate for producing the commercial preparation of phytase.