This chemical diversity and functionality can be further enhanced by the inclusion of nonnatural amino acids [5].

However, it is important to note that combinatorial peptide chemistry cannot cover a significant part of the peptide diversity when peptides are longer than a few amino acids .

In our context, strings are sequences of amino acids .

It was however observed that kernels for large molecules such as proteins were not suitable for smaller amino acid sequences such as peptides [14].

Indeed, the idea of gaps in the local-alignment kernel or in the Smith-Waterman algorithm is well suited for protein homology, but a gap of only a few amino acids in a peptide would have important consequences on its ability to bind with a target protein.

In contrast to classification and regression, the task we consider here (described in the next section) is ultimately to predict a string of amino acids .

Each entry in the downloadable dataset contains at least a nucleotide sequence or a list of amino acid substitutions.

Gag sequences were downloaded using the following settings through the standard search interface from http://www.hiv.lanl.gov/content/sequence/HIV/mainpage.html: virus: HIV-1; subtype: B; culture method: any; Only drug naive sequences: checked; genomic region: Gag (searching with amino acid indeX 790—2292 results in identical results).

In our study, for each pair of positions, we construct a 2X2 probability table representing the probabilities of observing both wildtype residues, a single amino acid substitution at the first position, a single amino acid substitution at the second position, and amino acid substitutions at both positions.

Typically, this type of analysis has been done by examining the one and two-site amino acid frequency counts at each position in multiple sequence alignments.

Although we considered the simplest such procedure, which involves estimating bounds on the four pair probabilities (M, M), (M, W), (W, M), and (W, W), where W denotes the consensus amino acid and M denotes any amino acid substitution, similar to [4,38], this procedure can be expanded to consider pairs of all individual amino acid substitutions instead of grouping all substitutions together.

As inhibitor potency increases, mutation pathways which confer resistance become more compleX and involve more amino acid substitutions to compensate for major resistance mutations.

These studies allowed examination of the patterns of single amino acid substitutions in Gag and their correlations with repeated PI-therapy failure.

A recent report has evaluated the viral fitness effects of single amino acid substitutions in CA [29].

found that ~5% of all possible amino acid CA substitutions resulted in viruses that replicate in vivo.

However using MCPU we were able to efficiently explore stabilities of all possible point mutants for an essential enzyme of a typical size (159 amino acids ) in a manageable amount of computational time (approx.

The likely explanation of the distinction between an apparent tradeoff when mutations are made in the active site and the opposite trend for mutations outside of the active site is that “carving” an active site requires special selection of catalytic amino acids , which could indeed have a destabilizing effect, overall.

Where i denotes the mutated amino acid and (p1- is the (p-Value for residue 1' which determines the fraction of interactions that this residue forms in the folding/unfolding transition state [40,43,44].

We compared the minimum and maximum simulated Tm values obtainable by mutating a single residue to any of the 19 other amino acids (Fig.

Apparently, protein loci where mutations can cause significant stabilization are statistically less susceptible to destabilizing mutations and vice versa, which may be expected: once a residue is already at its most stabilizing amino acid variant, the protein cannot be stabilized further by mutation.

This can therefore be directly compared to the protein world, constructed purely from simple amino acids .

The reaction mechanism of inverting glycosyltransferases is well understood and both experiments and molecular modeling support a direct displacement SNZ-like mechanism with a protein amino acid functioning as a catalytic base.

In this mechanism, a suitably positioned amino acid residue functioning as the catalytic base is required and two enzymes, namely a-1,3-galac-tosyltransferase [6] (a3GalT) and blood-group A and B 0:—1,3-galactosyltransferase [7] were proposed to proceed with this mechanism.

It is composed of a cyclic polypeptide ring and a branched fatty acid tail, and among the amino acids forming the peptide segment are the irregular amino acids D-Phenylalanine (DPhe) and 0c, y-Diamino Butyric acid (DAB).

The five non-cyclized DAB amino acids each carry a charge of +1, and thus the cationic peptide has a total charge of +5 [6].

The peptides are thought to fulfil the initial stages of their bactericidal activity by anchoring themselves to the bacterial membrane via the DAB amino acids [12, 13].