3. Results and discussions

### 3.1 Complex structures from EM maps

Deriving high-resolution molecular assembly structures from microscopy maps are a major application of the map approach. This method has been successfully applied into several experimental studies [12, 13]. Figure 4 illustrates the steps to perform a fitting of high-resolution molecular structure into electron

Figure 4.

Steps to derive molecular assembly structures by fitting molecular structures into electron microscopy maps.

## Protein-Protein Docking Using Map Objects DOI: http://dx.doi.org/10.5772/intechopen.83543

E desolv <sup>12</sup> <sup>¼</sup> <sup>s</sup>δ<sup>2</sup>

minimums.

Figure 4.

70

<sup>1</sup> ∑ m<sup>1</sup>

υ = 0.14 kcalÅ, b = 330 kcal/(C<sup>2</sup>

2.7 Conformational search

3. Results and discussions

3.1 Complex structures from EM maps

δ3

Molecular Docking and Molecular Dynamics

where s is the desolvation parameter.

0 @

C1e<sup>2</sup> 1

> <sup>1</sup> <sup>þ</sup> <sup>C</sup><sup>6</sup> 2

be derived from atomic force field or from experimental data. By fitting into energies calculated with the CHARMM force field [11], we obtained the parameters

� � � <sup>C</sup>2e<sup>2</sup>

δ3 <sup>2</sup> <sup>1</sup> <sup>þ</sup> <sup>C</sup><sup>6</sup> 1 � � <sup>1</sup> <sup>þ</sup> ð Þ <sup>C</sup>2=<sup>2</sup> <sup>6</sup> � �

These interaction parameters used to define the interactions, Eqs. (20)–(23), can

Å), and s = 70 kcal/(C<sup>2</sup>

We implemented the grid-threading Monte Carlo searching algorithm [10] for robustly fitting rigid domains to a target map. The grid-threading Monte Carlo (GTMC) search is a combination of the grid search and Monte Carlo sampling. As shown in Figure 3, the conformational space is split into grid points, and short Monte Carlo searches are performed to identify local maximums around the grid

Deriving high-resolution molecular assembly structures from microscopy maps are a major application of the map approach. This method has been successfully applied into several experimental studies [12, 13]. Figure 4 illustrates the steps to perform a fitting of high-resolution molecular structure into electron

Steps to derive molecular assembly structures by fitting molecular structures into electron microscopy maps.

2

Å2 ). 1

A (23)

<sup>1</sup> <sup>1</sup> <sup>þ</sup> ð Þ <sup>C</sup>1=<sup>2</sup> <sup>6</sup> � �

points. The global maximum is identified among the local

microscopy maps. We chose a T-cell receptor (TCR) variable domain (PDB code: 1a7n) as an example complex to illustrate the modeling process with map objects. The TCR variable domain is a complex of two chains, α-chain and β-chain. The two chains are first blurred into maps of the same resolution (here 15 Å) as the EM map. Then each map is fitted into the EM map to get a complex map. The complex map is projected back to atomic structures, which is the complex structure we are looking for. The root mean square (rms) deviation of the fitting result from X-ray complex is 3 Å.

The structure obtained from map fitting generally is not optimized in atomic details. There are often atom overlaps or improper spacing between components. This structural mismatch can be removed by many modeling methods available in CHARMM [14, 15], such as energy minimization and simulated annealing, if the fitting result is very close to the right structure. After the minimization, the rms deviation is 0.97 Å.
