mathematics-

Analysis of the mode of interaction between ligands and their target proteins is of crucial importance in order to explore different aspects of biochemical processes. Besides laboratory experiments, there is an emerging role of in-silico methods in investigating the interactions of ligands to proteins.

In-silico study of protein-ligand interaction involves molecular docking, where the binding energy and geometry of ligands, substrates or possible drug candidates to target proteins is predicted using computational chemistry methods.

The task in molecular docking assignments is to find the best ligand protein complex geometry. The problem is usually seen as an optimization task where the goal is to minimize the intermolecular interaction energy between the two molecules of interest. Since the possible number of ligand- protein complex geometry is usually very large, different algorithms are used in order to accurately explore the space of possible conformations while decreasing the computational power needed for the docking calculation at the same time.

Thus, a molecular docking calculation consists of the following steps:

(1) Optimization of the ligand geometry, calculate pH-dependent partial charges, identify rotatable bonds and

(2) Calculate electrostatic properties of the protein of interest and define the ligand-binding region,

(3) The ligand-protein interaction is then calculated by a scoring function that includes terms and equations that describe the intermolecular energies. The result of a docking calculation is a ligand-protein complex geometry and the corresponding binding energy. Therefore, for accurate interpretation of the results, a high-quality representation of the complex geometry is of great importance as well

(4)DockingServer integrates a number of computational chemistry software specifically aimed at correctly calculating parameters needed at different steps of the docking procedure, i.e. accurate ligand geometry optimization, energy minimization, charge calculation, docking calculation and protein-ligand complex representation.

Thus, the use of DockingServer allows the user to carry out highly efficient and robust docking calculation, which could not be achieved using single software so far. Since the calculations run on our servers, the use of DockingServer does not require powerful hardware or pre-installed software from the user.

The core of DockingServer web application is our integrating PHP software connected to a MySQL database, where the different tasks are automatically managed by daemons running on our servers and the input data will be read from the database and output data will be directed into the database.

The AutoGrid/AutoDock 4.0 (Morris, et al., 1998) program package is used for docking calculations, allowing docking of flexible ligands to proteins. With the help of Autodock program package the partial charges and atom types of the ligand and proteins can be assigned. However, the results of docking calculations strongly depend on the accuracy of charges calculated in the ligand.

Thus, besides offering ligand partial charge calculation with the Auto-Dock program package DockingServer also integrates calculator plug-ins from Chemaxon (Csizmadia, 2000) and the MOPAC2007 program (Stewart, 2007) for accurate pH-dependent protonation and ligand partial charge calculation. Moreover, geometry optimization, refinement of the ligand geometry using semiempirical methods (PM6) can be carried out. Automatic conversions between necessary file formats are achieved by Chemaxon tools.

For more information on molecular docking, visit http://www.dockingserver.com

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We've been told that attitude is everything. Is it really? Is everything we do successfully or unsuccessfully based on our attitude? The famous psychologist William James said, "The greatest discovery of any generation is that a human being can alter his life by altering his attitude."

Great advice. But the question is, how do we know if we need a change in attitude? If you are not living the kind of life that brings you satisfaction, joy, and abundance, then jump on the "Attitude Change Wagon" now.

Ponder this: When we change how we think about something, the thing we are thinking about changes. (Please read this sentence again.)

It's easy to say "Change your attitude and change your life" but how do you do that and how easy is it? You may not call it easy but it does not have to be difficult if you use a few proven strategies. If you desire to be happier, more joyful, have more abundance, have less stress, and want to really live your dreams, why not give these simple techniques a try?

Think of a person you know who has a great attitude. They are probably up-beat, they think in terms of possibilities, they are non-critical,
they laugh often, and they are great to be around.

Check your attitude with the 'mirror technique'. Observe the reactions of the people you live and.work with throughout the day If they are less than open, a little down, or grumpy, that could be a reflection of your attitude. Attitudes are contagious.

Think with the end in mind. See yourself as that joyful, upbeat, successful,
person you are on the way to becoming. Understand that everything you need in order to live your dreams is already here.
Stop taking yourself so seriously. Look for the humor in all situations.
Get busy giving someone else a helping hand.

Remember that things take time. In most cases you will get immediate results, but if you don't, DO NOT GIVE UP. It will come.

If you are not getting the results you want in any area of your life, do an attitude check on yourself. Even better, have a friend give you some feedback on how you come across to others. This kind of knowledge is power. You can now flip the attitude switch to 'on' and change how you look at things so the things that you look at will change. You will then have an endless supply of Green Lights before you.

'I take nothing for granted. I now have only good days, or great days.'
--Lance Armstrong

Allan and Barbara Kenyon are Personal and Business Coaches who help their clients live their dream life. Allan was a certified instructor for eighteen years with the Carnegie organization and he received coach training with Coach Training Institute. Barbara holds a Masters Degree in Counseling and is a Graduate of Coach U. The Kenyons work with success-minded men and women who want to achieve their personal or professional goals faster than if they were to go it alone. Their clientele include professionals, executives, entrepreneurs, business owners, sales people, and people in transition. Their coaching focuses on goals in the areas of career, money, retirement, health, relationships, getting organized, and life balance.

The Kenyons offer a 30 minute complimentary telephone coaching session so potential clients can decide if their coaching is for them. They can be reached at 402-423-6777 or by E-mail at KenyonCoaching@aol.com Their website is http://www.kenyoncoaching.com