Protein Modelling
The Protein Modelling Laboratory works on molecular modelling of proteins using physical methods. Our areas of work range from basic research in modelling methodologies to applications with biotechnological and biomedical interest.
Head of Laboratory
Cláudio M. Soares | Research InterestsGroup MembersSelected PublicationsModelação de Proteínas (PT) | |
Phone (+351) 214469610 | |
Research Interests
The Protein Modelling Laboratory works on molecular modelling of proteins using physical methods. Our areas of work range from basic research in modelling methodologies to applications with biotechnological and biomedical interest. Modelling redox proteins and redox chains is one of our research interests, and one of the most relevant examples was the work, together with the Molecular Simulation Laboratory, on the mechanisms of [NiFe] hydrogenase, which catalyses the reversible molecular hydrogen cleavage into electrons and protons. Hydrogen permeation towards the internal active site was investigated by molecular dynamics simulations of the enzyme in solution. We were able to observe permeation events, highlighting the presence of channels. These channels lead hydrogen towards the Ni atom, and contain several bottlenecks, like a valine residue near the active site, which when mutated in silico to an alanine, showed improved hydrogen access. Another important aspect on the mechanism of [NiFe]-hydrogenase is the proton transfer process. Produced protons have to reach the surface of the enzyme and ionisable groups are required for an efficient proton transfer. Using continuum electrostatic and Monte Carlo simulations, we investigated the protonation events and we were able to propose proton transfer pathways. In collaboration with other groups at ITQB we are trying to understand the mechanism of laccases at the molecular level. Studying enzymes in non-aqueous solvents is another important area in our laboratory, with focus on the molecular mechanisms of enzyme hydration, enantioselectivity and catalysis. Ionic liquids are a new type of non-aqueous solvents with interesting properties for enzyme catalysis, but the molecular mechanisms present are largely unknown. We published a parametrisation of two ionic liquids, which captures both the static and dynamic properties of these media. These liquids we then used in protein simulations, for the first time to our knowledge, clarifying the behaviour of these systems at the molecular level. Another work related with biotechnology are our simulations studies trying to understand the effect of negatively charged compatible solutes on protein stabilization. ABC transporters constitute a new topic to our laboratory. Our first work on the subject was on the NBD1-NBDassociation in CTFR, the chloride transporter involved in cystic fi brosis, one of the most common genetic diseases. We built structural models for this association, responsible for ATP hydrolysis, and used them to understand the effect of mutations on disease causing genotypes. Right now we are studying the ATP-dependent “power stroke”, in order to understand molecular architecture and functionality of such transporters.
Group Members
Bruno Victor, Post-doc
Ana Sofia Oliveira, PhD student
Diana Lousa, PhD student
João M. Damas, PhD student
Selected Publications
- Micaelo, NM, Victor, BL, Soares, CM (2008) “Protein thermal stabilization by charged compatible solutes. Computational studies in rubredoxin from Desulfovibrio gigas”, Proteins, accepted
- Roxo-Rosa M., Xu Z., Schmidt A., Neto M., Cai Z. W., Soares C. M., Sheppard D. N. and Amaral M. D. (2006). “Revertant mutants G550E and 4RK rescue cystic fibrosis mutants in the first nucleotide-binding domain of CFTR by different mechanisms.” Proceedings of the National Academy of Sciences of the United States of America 103(47): 17891-17896
- Teixeira V. H., Baptista A. M. and Soares C. M. (2006). “Pathways of H-2 toward the active site of [NiFe]-hydrogenase.” Biophysical Journal 91(6): 2035-2045
Laboratory's Website
For further information please visit the laboratory's website
Modelação de Proteínas (PT)
O Laboratório de Modelação de Proteínas desenvolve investigação na área da simulação física de proteínas, tentando compreender processos biológicos utilizando meios computacionais, ou em colaboração com grupos de investigação experimental. O objectivo final destas investigações é a compreensão da Vida ao nível molecular e atómico, pela simulação dos seus mais pequenos componentes. O trabalho do Laboratório de Modelação de Proteínas centra-se no estudo de proteínas envolvidas em cadeias transportadoras de electrões, e em processos com interesse biotecnológico e biomédico.
