Recent experiments have called into question the assumption of a random A-site distribution in mixed-valence colossal magnetoresistance (CMR) manganites. We explored the possibility of an A-site (La(3+)/Sr(2+)) ordering in a CMR manganite La(3/4)Sr(1/4)MnO(3) using molecular dynamics (MD) simulations with a newly developed force field (FF) and quantum mechanics (QM) (density functional theory with the generalized gradient approximation) calculations of the relative stability of structures obtained from MD. Both methods suggest that the degree of stabilization (enthalpy gain) of A-site ordering is not sufficient to overcome the accompanying entropy loss, supporting the assumption of a random A-site distribution in La(3/4)Sr(1/4)MnO(3). This approach combining MD and QM as well as the versatile FF developed in this study should be useful for investigating the structure and functionality of magnetic tunnel junction devices involving composite materials of mixed-valence manganites.