Building Structural Models

We focus on four interrelated aspects of protein-protein and protein-nucleic acid interactions. Section 2 deals with building structural models for protein complexes. In Section 3 we present an overview of the various methods for computing contributions to the stability of protein complexes. In Section 4 the focus shifts to the rates of forming protein complexes. Finally in Section 5 we discuss the impacts of protein dynamics on the structures, thermodynamics, and kinetics of protein complexes. 

As a result of favorable interactions, a protein and its partner(s) will form a stereospecific complex. Under favorable conditions, the structure of this complex can be determined by X-ray crystallography, NMR, or electron microscopy. The structure holds the key to understanding the interactions involved and is the basis for making computations on the stability and rate of complex formation. 

In many cases, for practical or technical reasons (as opposed to any fundamental physical reasons), the structures of protein complexes cannot be determined experimentally. If the structure of a protein complex with adequate sequence similarity is available, one can build the structure of a query complex by homology modeling [1-3]. The applicability of homology modeling to protein complexes is still limited because the current structural database provides only a sparse coverage of the protein interaction space. 

We briefly mention two related subjects. For obvious reasons, the interfaces of protein complexes have been a target for developing drug molecules. This subject 

---

Advancements in crystallography/NMR techniques have resulted in an exponential increase in the number of protein structures in publicly available structural databases (e.g., as of September 2009, the Protein Database Bank PDB contains experimentally solved 3D structural data for 60,000 structures (www.pdb.org)). In addition, several structural genomics consortiums aim to provide crystal structures across all protein families (38). In case when experimental structures are not available, techniques such as homology modeling are often used to build structural models of other homologous proteins (21). 

The method of building predictive models in QSPR/QSAR can also be applied to the modeling of materials without a unique, clearly defined structure. Instead of the connection table, physicochemical data as well as spectra reflecting the compound s structure can be used as molecular descriptors for model building,... 

Write structural formulas or build molecular models and give the... 

Write structural formulas or build molecular models and give the functional class and substitutive names of all the isomeric alcohols that have the molecular formula C4H10O... 

Wnte structural formulas or build molecular models for all the constitutionally isomenc alcohols of molecular formula C5H12O Assign a substitutive and a functional class name to each one and specify whether it is a pnmary secondary or tertiary alcohol... 

Give the structures or build molecular models of both alcohol products for each ketone... 

All current comparative modeling methods consist of four sequential steps (Fig. 2) [5,6]. The first step is to identify the proteins with known 3D structures that are related to the target sequence. The second step is to align them with the target sequence and pick those known structures that will be used as templates. The third step is to build the model... 

Figure 3 Model building by Modeller [31], First, spatial restraints in the form of atomic distances and dihedral angles are extracted from the template stmcture(s). The alignment is used to determine equivalent residues between the target and the template. The restraints are combined into an objective function. Finally, the model for the target is optimized until a model that best satisfies the spatial restraints is obtained. This procedure is technically similar to the one used in structure determination by NMR.

In reality, heat is conducted in all three spatial dimensions. While specific building simulation codes can model the transient and steady-state two-dimensional temperature distribution in building structures using finite-difference or finite-elements methods, conduction is normally modeled one-... 

Hydride reduction (with LiAlH4 or NaBH4) of each of the following ketones has been reported in the chemical literature and gives a mixture of two diastereomeric alcohols in each case. Give the structures or build molecular models of both alcohol products for each ketone. 

---