my %acgt = (
   A => '00',
   C => '01',
   G => '10',
   T => '11',
);

sub encode {
    my $string = uc shift;
    (my $bin = $string) =~ s/(.)/$acgt{$1}/g
    return pack 'B*', $bin;
}

my $lookup = '';
while( <SMALLFILE> ) {
    chomp;
    $lookup{encode($_)} = 1;
}

while( <BIGFILE> ) {
    chomp;
    print if $lookup{encode($_)};
}