Recognition of alpha-helix transmembrane domains with an amphipathy scale generated by molecular dynamics using only the primary sequence of proteins.

We recently developed an amphipathy scale, elaborated from molecular dynamics data that can be used for the identification of hydrophobic or hydrophilic regions in proteins. This amphipathy scale reflects side chain/water molecule interaction energies. We have now used this amphipathy scale to find candidates for transmembrane segments, by examining a large sample of membrane proteins with alpha-helix segments. The candidates were selected based on an amphipathy coefficient value range and the minimum number of residues in a segment. We compared our results with the transmembrane segments previously identified in the PDB_TM database by the TMDET algorithm. We expected that the hydrophobic segments would be identified using only the primary structures of the proteins and the amphipathy scale. However, some of these hydrophobic segments may pertain to hydrophobic pockets not included in transmembrane regions. We found that our amphipathy scale could identify alpha-helix transmembrane regions with a probability of success of 76% when all segments were included and 90% when all membrane proteins were included.

Recognition of alpha-helix transmembrane domains with an amphipathy scale generated by molecular dynamics using only the primary sequence of proteins

We recently developed an amphipathy scale, elaborated from molecular dynamics data that can be used for the identification of hydrophobic or hydrophilic regions in proteins. This amphipathy scale reflects side chain/water molecule interaction energies. We have now used this amphipathy scale to find candidates for transmembrane segments, by examining a large sample of membrane proteins with alpha-helix segments. The candidates were selected based on an amphipathy coefficient value range and the minimum number of residues in a segment. We compared our results with the transmembrane segments previously identified in the PDB_TM database by the TMDET algorithm. We expected that the hydrophobic segments would be identified using only the primary structures of the proteins and the amphipathy scale. However, some of these hydrophobic segments may pertain to hydrophobic pockets not included in transmembrane regions. We found that our amphipathy scale could identify alpha-helix transmembrane regions with a probability of success of 76% when all segments were included and 90% when all membrane proteins were included.

The role of viral and cellular proteins in the budding of human immunodeficiency virus.

For over two decades, research on Human immunodeficiency virus (HIV), which is responsible for AIDS, has aimed at understanding of the molecular mechanisms used by this virus during its life cycle. An essential step in the HIV life cycle is the budding, which promotes the release of viral particles from the host cell. It has recently been revealed that HIV in the process of budding uses besides one viral protein also the machinery of the infected cell, in particular the proteins Tsg101 and ubiquitin. The viral protein is the p6 domain of the Gag precursor polyprotein. In normal cells, Tsg101 functions as a regulator of endocytic trafficking that recognizes ubiquitinated cargo and directs its delivery to degradative compartments. In HIV-infected cells, Tsg101 and ubiquitin interact with Gag p6 to promote the release of new viral particles from the host cell. Molecular mechanisms underlying the process of HIV budding from infected cells suggests a whole new range of drug targets that could prove useful in AIDS suppression in HIV-positive patients.

A new amphipathy scale I. Determination of the scale from molecular dynamics data.

Two new amphipathy scales elaborated from molecular dynamics data are presented. Their applications contribute for the identification of the hydrophobic or hydrophilic regions in proteins solely from the primary structure. The new amphipathy coefficients (AC) reflect the side chain/solvent molecules configurational energies. A polar (water) and an apolar solvent, CCl4, were used resulting in the two ACwater and ACCCl4 scales. These solvents were chosen to simulate the aqueous phases and the transmembrane ambients of cellular membranes where the membrane proteins act. The new amphipathy scales were compared with some previous scales determined by different methods, which were also compared between them, indicating more than 90% of the correlation coefficients are less than 0.9: the scales are strictly dependent on the methodologies used in their determination. The ACCCl4 scale is related with the size of side chain amino acids while ACwater is related with the hydrophobicity of side chain amino acids. The quality of the scales was confirmed by an example of application where ACwater was able to identify correctly the transmembrane, hydrophobic regions of a membrane protein. These results also indicate that water is an important factor responsible for the tertiary structure of membrane proteins.