Drugs and receptor interaction (ionic, covalence, H and VDN force)
INTRO
Most drugs combine with specific sites on macromolecules (e.g. cell membrane components, enzymes, proteins) by precise physiochemical and steric interactions between specific chemical groups of the drug. These sites are termed receptors. The interaction need force such as ionic force, covalence force, hydrogen force and van der waal force.
IONIC FORCE
An ionic bond is an electrical attraction between two oppositely charged atoms or groups of atoms. Normally, atoms are neutral and have no charge. However, in order to gain stability they will sacrifice their neutrality by either losing one or more of its outermost electrons thus becoming a positive ion (cation) or they will gain one or more electrons thus becoming a negative ion (anion). Once this has happened, the resulting charged atoms will attract each other. That electrical attraction between two oppositely charged ions is referred to as an ionic bond. All salts are ionic.
COVALENCE FORCE
Force holding atoms in a molecule together as a specific, separate entity. In covalent bonds, two atoms share one or more pairs of valence electrons to give each atom the stability found in a noble gas. In single bonds, one electron pair is shared. In coordinate covalent bonds, additional electron pairs are shared with another atom, usually forming a functional group, such as sulfate (SO4) or phosphate (PO4).
HYDROGEN FORCE
Hydrogen bonds occur between molecules that have a hydrogen covalently bonded with an oxygen, nitrogen, or fluorine atom. When the other end of that covalent bond is a hydrogen, the electronegative atom is pulling all electrons associated with hydrogen away from it. Hydrogen acts almost as a positive charge. This high charge makes hydrogen bonds a very strong type of dipole-dipole force. Substances which hydrogen bond are typically liquids at room temperature.
VAN DER WAALS FORCE
Water molecules in liquid water are attracted to each other by electrostatic forces, and these forces have been described as van der Waals forces. Even though the water molecule as a whole is electrically neutral, the distribution of charge in the molecule is not symmetrical and leads to a dipole moment. This leads to a net attraction between such polar molecules which finds expression in the cohesion of water molecules and contributes to viscosity and surface tension.
Wednesday, February 3, 2010
Saturday, January 16, 2010
Tuesday, January 12, 2010
summary from CADD class for 4weeks...
1)Protein sequence
Protein sequence can be done by using MEROPS. The MEROPS database is a resource for information on peptidases (sometimes also termed proteases, proteinases and proteolytic enzymes). MEROPS also includes the proteins that inhibit peptidase.
About 3000 individual peptidases and inhibitors are included in the database and its describes the classification and nomenclature of the peptidase or inhibitor, and provides links to supplementary pages showing sequence identifiers, the structure if known, literature references and more.The MEROPS database uses hierarchical, structure-based schemes for the classification of the peptidases and inhibitors. Each is assigned to a Family on the basis of statistically significant similarities in amino acid sequence, and families that are thought to be homologous are grouped together in a Clan.
figure 1: protein sequence by MEROPS
2)blast
Basic Local Alignment Search Tool, or BLAST, is an algorithm for comparing primary biological sequence information, such as the amino-acid sequences of different proteins or the nucleotides of DNA sequences. A BLAST search enables a researcher to compare a query sequence with a library or database of sequences, and identify library sequences that resemble the query sequence above a certain threshold. For example, following the discovery of a previously unknown gene in the mouse, a scientist will typically perform a BLAST search of the human genome to see if humans carry a similar gene; BLAST will identify sequences in the human genome that resemble the mouse gene based on similarity of sequence.
figure 2: BLAST(lon)
3)CLUSTAL X
CLUSTAL X is a interface for the widely-used progressive multiple sequence alignment program CLUSTAL W. The new system is easy to use, providing an integrated system for performing multiple sequence and profile alignments and analysing the results. CLUSTAL X displays the sequence alignment in a window on the screen. A versatile sequence colouring scheme allows the user to highlight conserved features in the alignment. Pull-down menus provide all the options required for traditional multiple sequence and profile alignment. New features include: the ability to cut-and-paste sequences to change the order of the alignment, selection of a subset of the sequences to be realigned, and selection of a sub-range of the alignment to be realigned and inserted back into the original alignment. Alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted. Quality analysis and realignment of selected residue ranges provide the user with a powerful tool to improve and refine difficult alignments and to trap errors in input sequences.
4)Blast pdb
The Protein Data Bank (PDB) archive is the single worldwide repository of information about the 3D structures of large biological molecules, including proteins and nucleic acids. These are the molecules of life that are found in all organisms including bacteria, yeast, plants, flies, other animals, and humans. Understanding the shape of a molecule helps to understand how it works. This knowledge can be used to help deduce a structure's role in human health and disease, and in drug development. The structures in the archive range from tiny proteins and bits of DNA to complex molecular machines like the ribosome.
figure 3: 3D structure of 1RR9
Protein sequence can be done by using MEROPS. The MEROPS database is a resource for information on peptidases (sometimes also termed proteases, proteinases and proteolytic enzymes). MEROPS also includes the proteins that inhibit peptidase.
About 3000 individual peptidases and inhibitors are included in the database and its describes the classification and nomenclature of the peptidase or inhibitor, and provides links to supplementary pages showing sequence identifiers, the structure if known, literature references and more.The MEROPS database uses hierarchical, structure-based schemes for the classification of the peptidases and inhibitors. Each is assigned to a Family on the basis of statistically significant similarities in amino acid sequence, and families that are thought to be homologous are grouped together in a Clan.
figure 1: protein sequence by MEROPS
2)blast
Basic Local Alignment Search Tool, or BLAST, is an algorithm for comparing primary biological sequence information, such as the amino-acid sequences of different proteins or the nucleotides of DNA sequences. A BLAST search enables a researcher to compare a query sequence with a library or database of sequences, and identify library sequences that resemble the query sequence above a certain threshold. For example, following the discovery of a previously unknown gene in the mouse, a scientist will typically perform a BLAST search of the human genome to see if humans carry a similar gene; BLAST will identify sequences in the human genome that resemble the mouse gene based on similarity of sequence.
figure 2: BLAST(lon)
3)CLUSTAL X
CLUSTAL X is a interface for the widely-used progressive multiple sequence alignment program CLUSTAL W. The new system is easy to use, providing an integrated system for performing multiple sequence and profile alignments and analysing the results. CLUSTAL X displays the sequence alignment in a window on the screen. A versatile sequence colouring scheme allows the user to highlight conserved features in the alignment. Pull-down menus provide all the options required for traditional multiple sequence and profile alignment. New features include: the ability to cut-and-paste sequences to change the order of the alignment, selection of a subset of the sequences to be realigned, and selection of a sub-range of the alignment to be realigned and inserted back into the original alignment. Alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted. Quality analysis and realignment of selected residue ranges provide the user with a powerful tool to improve and refine difficult alignments and to trap errors in input sequences.
4)Blast pdb
The Protein Data Bank (PDB) archive is the single worldwide repository of information about the 3D structures of large biological molecules, including proteins and nucleic acids. These are the molecules of life that are found in all organisms including bacteria, yeast, plants, flies, other animals, and humans. Understanding the shape of a molecule helps to understand how it works. This knowledge can be used to help deduce a structure's role in human health and disease, and in drug development. The structures in the archive range from tiny proteins and bits of DNA to complex molecular machines like the ribosome.
figure 3: 3D structure of 1RR9
