USING MOLECULAR-DYNAMICS TO PREDICT FACTORS AFFECTING BINDING STRENGTH AND MAGNETIC RELAXIVITY OF MRI CONTRAST AGENTS

We demonstrate the use of molecular dynamics and molecular mechanics m ethods to calculate properties and behavior of metal-chelate complexes that can be used as MRI contrast agents. Static and dynamic propertie s of several known agents were calculated and compared with experiment . We calculated the static properties such as the q-values(number of i nner shell waters) and binding distances of chelate atoms to the metal ion for a set of chelates with known X-ray structure. The dynamic fle xibility of the chelate arms was also calculated. These computations w ere extended to a series of exploratory chelate structures in order to estimate their potential as MRI contrast agents. We have also calcula ted for the first time the NMR relaxivity of an MRI contrast agent usi ng a long (5 nsec) molecular dynamics simulation. Our predictions are promising enough that the method should prove useful for evaluating no vel candidate compounds before they are synthesized. One novel static property, the projected area of chelate atoms onto a virtual surface c entered on the metal ion (gnomonic projection), was found to give an e ffective measure of how well the chelate atoms use the free space arou nd the metal ion.